XIAP Cancer Research Results
XIAP, X-linked inhibitor of apoptosis protein (XIAP) baculoviral IAP repeat-containing protein 4 (BIRC4): Click to Expand ⟱
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Also known as BIRC4. XIAP is inhibited by DIABLO (Smac) and HTRA2 (Omi), two death-signaling proteins released into the cytoplasm by the mitochondria.
High proportions of XIAP may function as a tumor marker. In developing prostate cancer, XIAP is one of four IAPs overexpressed in the prostatic epithelium.
XIAP functions predominantly as a protumorigenic protein in the context of cancer. Its upregulation is commonly observed in various tumor types and is associated with poor patient outcomes and resistance to therapy due to its potent inhibition of apoptosis.
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Scientific Papers found: Click to Expand⟱
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in-vitro, |
BC, |
MCF7 |
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in-vitro, |
BC, |
T47D |
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Bacteria↓, Nowadays, silver nanoparticles (AgNP) are widely used in the medical field mainly for their antibacterial properties
Apoptosis↑, AgNP of 2 (AgNP2) and 15 nm (AgNP15) induce apoptosis in human MCF-7 and T-47D breast cancer cells.
ER Stress↑, Treatment with AgNP2 and AgNP15 led to accumulation and aggregation of misfolded proteins causing an endoplasmic reticulum (ER) stress and activating the unfolded protein response (UPR).
UPR↑,
PERK↑, The three main ER sensors, PERK, IRE-1α and ATF-6, were rapidly activated in response to AgNP2 and AgNP15
IRE1↑,
ATF6↑,
ATF4↑, AgNP2 and AgNP15 induced upregulation of the transcription factors ATF-4 and GADD153/CHOP
CHOP/DDIT3↑,
Casp9↑, Moreover, the initiating caspase-9 and the effector caspase-7 were activated in response to these NPs.
Casp7↑,
Mcl-1↓, In contrast, a downregulation of Mcl-1 and xIAP protein expression as well as a processing of PARP were observed.
XIAP↓,
PARP↝,
selectivity↑, Of note, the non-cancerous MCF-10A cells were more resistant to both AgNP2 and AgNP15 when compared to MCF-7 and T-47D cell lines.
TumCP↓,
TumCCA↑,
Apoptosis↑,
STAT3↓,
Akt↓,
P21↑,
BAX↑,
cycD1/CCND1↓,
cycE/CCNE↓,
survivin↓,
XIAP↓,
Bcl-2↓,
eff↑, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment.
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in-vivo, |
Pca, |
PC3 |
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in-vivo, |
Pca, |
DU145 |
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XIAP↓, dose dependent
survivin↓,
Bcl-xL↓,
Bcl-2↓,
BAX↑,
angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2/PTGS2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,
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BC, |
MCF7 |
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NA, |
BC, |
MDA-MB-231 |
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Nor, |
HMEC |
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Apoptosis↑,
ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
DNAdam↑,
OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
Bcl-2↓,
XIAP↓,
survivin↓,
DR5↑,
IKKα↓,
NF-kB↓,
selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS
selectivity↑, WS was shown to impede the growth of new cancer cells, but not normal cells,
ROS↑, help induce programmed death of cells by generating reactive oxygen species (ROS), and sensistize cancer cells to apoptosis
Apoptosis↑,
ChemoSen↑, Pre-clinical studies in several cancer types have shown up to 80% inhibition using combination chemotherapy [19].
RadioS↑, It was not until 1996, that WFA’s radiosensitizer activity was reported that caused V79 cell survival reduction where 1-h pre-treatment at 2.1 µM dose before radiation significantly killed cells
NF-kB↓, inhibiting NF-κB activation
ER-α36↓, WFA, it was found the phytochemical downregulated the estrogen receptor-α (ER-α) protein in MCF-7 cells.
P53↑, WFA selectively activated p53 in tumor cells treated with the leaf extract of Ashwagandha [71] leading to growth arrest and apoptosis.
*ROS∅, opposed to the normal human mammary epithelial cells (HMEC) [72] which did not increase ROS production.
γH2AX↑, The group found an increase in γ-H2AX and number of cells expressing the phosphorylated form which is a marker for DNA damage in WFA treated MCF-7 cells.
DNAdam↑,
MMP↓, As ROS is well known to affect mithochondrial membrane potential, they found a change in mitochondrial membrane potential and altered mitochondrial morphology in WFA treated cells.
XIAP↓, XIAP (X-linked inhibitor of apoptosis protein), cIAP-2 (cellular inhibitor of apoptosis protein-2) and Survivin proteins were found to be reduced in MDA-MB-231 and MCF-7 cells when treated with WFA
IAP1↓,
survivin↓,
SOD↓, figure 2
Dose↝, doses of 3 and 4 mg/kg and the authors found 59% reduction of tumor and polyp initiation and progression in the WFA treated mice compared to the controls [80].
IL6↓, WFA downregulated expression of inflammatory markers in these tumors such as IL-6, TNF-α, COX-2 along with pro-survival markers such as pAkt, Notch1 and NF-κβ [80].
TNF-α↓,
COX2/PTGS2↓,
p‑Akt↓,
NOTCH1↓,
FOXO↑, figure 3 prostrate cancer
Casp↑,
MMP2↓,
CSCs↓, WFA treatment significantly reduced ALDH+ CSC population, whereas Cisplatin treatment increased CSC population.
*ROS↓, WFA was found to increase cellular survival in simulated injury and in H2O2-induced cell apoptosis along with inhibition of oxidative stress.
*SOD2↑, Thus, via upregulation of SOD2, SOD3, Prdx-1 by H2O2, WFA treatment leads to inhibition of the antioxidants and Akt-dependent improvement of cardiomyocyte caspase-3 [103].
chemoP↑, First, given the safety record of WS, it can be used as an adjunct therapy that can aid in reducing the adverse effects associated with radio and chemotherapy due to its anti-inflammatory properties.
ChemoSen↑, Second, WS can also be combined with other conventional therapies such as chemotherapies to synergize and potentiate the effects due to radiotherapy and chemotherapy due to its ability to aid in radio- and chemosensitization, respectively.
RadioS↑,
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Lung, |
H1650 |
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Lung, |
A549 |
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CRC, |
HCT116 |
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MDA-MB-231 |
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PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP/DDIT3↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo
toxicity↓, Some sedation, ptosis and ataxia were observed in Sprague-Dawley rats 15–20 minutes of administering a herbal concoction that contained WS at a large dose of 1–2 g/kg body weight [36]
TumW↓, Induction of apoptosis by WA has been noted in some in vivo models where treatment with 4 mg/kg WA, i.p. 5 times for 2 weeks markedly reduced MDA-MB-231 tumor weights in nude mice as well as increased apoptosis compared to tumors in control mice [56
Dose?, 20 mg/kg, oral 3X/wk for 14 wk Hamster Head and Neck Example
eff↝, showed that this chemopreventive capacity was dependent on a circadian pattern where hamsters dosed with WA at 8 AM and 12 PM showed 100% protection from oral tumor formation while those treated at 12 AM showed 50% incidence in oral tumors
Ki-67↓, WA treatment resulted in retarded tumor growth; reduction in cell proliferation marker Ki-67, survivin, and XIAP,
survivin↓,
XIAP↓,
PERK↑, higher protein expression of pERK, pRSK, CHOP and DR-5 was also observed in the WA-treated group compared to control.
p‑RSK↑,
CHOP/DDIT3↑,
DR5↑,
Dose↝, Clinically diagnosed schizophrenia patients who had received antipsychotic medications for 6 months or more received either a capsule with 400 mg of WS extract (n=15), three times daily, for 1 month [80]
BG↓, Results after one month showed significant reduction in serum triglycerides and fasting blood glucose levels in the WS extract- treated group compared to the placebo
DNMTs↓, in MCF7 and MDA-MB-231 breast cancer cells WA treatment suppressed transcription of DNMT.
Apoptosis↑, Baicalein is thought to prevent cancer progression by inducing apoptosis, autophagy, and genome instability, and its ability to promote chemo-potentiation, anti-metastatic effects, and regulate specific signalling molecules and transcription factors.
TumAuto↑,
DNAdam↑,
*antiOx↑, Baicalein has already been proven to be a radical scavenger that acts as an antioxidant [14,15
Inflam↓, it can also reduce inflammation [16] and act as an E2 prostaglandin inhibitor [17].
PGE2↓,
TumCCA↑, Baicalein properties prevent cell proliferation, induce apoptosis, autophagy, cell cycle arrest, cancer cell migration and invasion, and decrease angiogenesis [18,19].
TumCMig↓,
TumCI↓,
angioG↓,
selectivity↑, Furthermore, some studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells.
ChemoSen↑, the current review emphasises baicaleins' synergistic potential with other chemotherapeutic agents
HIF-1↓, baicalein against ovarian cancer by demonstrating that it can limit tumour cell viability by downregulating the expression of cancer-promoting genes such as HIF-1, cMyc, NFkB, and VEGF
cMyc↓,
NF-kB↓,
VEGF↓,
P53↑, Baicalein has been shown to activate p53, a tumour suppressor protein that regulates cell growth and division [26].
MMP2↓, anticancer properties of baicalein are mediated through various molecular mechanisms, including inhibition of MMP-2;
CSCs↓, inhibition of cancer stem cells
Bcl-xL↓, after bladder cancer cells were treated with baicalein, the expression of antiapoptotic genes (Bcl2, Bcl-xL, XIAP, and survivin) was reduced, and cell viability was decreased [38].
XIAP↓,
survivin↓,
tumCV↓,
Casp3↑, upregulating the expression of caspase-3 and caspase-8 and decreased the BCL-2/BAX ratio [16]
Casp8↑,
Bax:Bcl2↑,
Akt↓, in lung cancer cells, apoptosis was induced through the downregulation of the Akt/mTOR signalling pathway [25].
mTOR↓,
PCNA↓, baicalein treatment promoted apoptosis in mice with U87 gliomas by downregulating PCNA expression, enhancing the expression of caspase-3 and caspase-9 and improving the Bax/Bcl-2 ratio
MMP↓, baicalein treatment of lung cancer cells caused a collapse of the mitochondrial membrane potential (MMP), an increase in ROS generation, and enhanced PARP, caspase 3, and caspase 9 cleavage,
ROS↑,
PARP↑,
Casp9↑,
BioAv↑, Baicalein has been found to enhance the cytotoxicity and bioavailability of certain cancer therapy drugs when combined [85]
eff↑, combination of baicalein with silymarin differentially decreased the viability of HepG2 cells, enhanced the proportion of cells in the G0/G1 phase, upregulated tumour suppressors such as Rb and p53 and CDK inhibitors, and downregulated cyclin D1, cyc
P-gp/ABCB1↓, By inhibiting P-glycoprotein (P-gp), baicalein can increase the accumulation of chemotherapeutic drugs within cancer cells [21]
BioAv↑, selenium–baicalein nanoparticles as a targeted therapeutic strategy for NSCLC. This strategy significantly improves the bioavailability of baicalein through several mechanisms.
selectivity↑, ome studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells
Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2/KDR/Flk1↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP
CDK1↓, graphical abstract
Cyc↓,
p27/CDKN1B↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP/DDIT3↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5
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in-vitro, |
CRC, |
HCT8 |
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in-vivo, |
NA, |
NA |
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ROS↑,
TumCP↓, 2-5X lower IC50 than normal BBR
XIAP↓,
TumCG↓,
*toxicity↓, 13-Cys-BBR Had No Kidney And Liver Toxicity
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Review, |
Var, |
NA |
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IBD, |
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Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1/CCL2↓,
PGE2↓,
COX2/PTGS2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2/PTGS2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents
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CRC, |
HCT116 |
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angioG↓, BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF)
VEGF↓,
TumVol↓, BCP showed a remarkable reduction in tumor size
HSP60/HSPD1↓, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions.
HTRA↓,
survivin↓,
XIAP↓,
P21↑,
TumCP↓, BCP Inhibited Proliferation and Migration of HUVECs
TumCMig↓,
TumCG↓, BCP Inhibited Tumor Growth in an HCT-116 Cells Transplanted Mouse Xenograft Mode
Dose↝, BCP was orally administered for a period of 8 weeks. BCP (100 mg/kg) showed a significant anti-tumor activity
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CRC, |
HCT116 |
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in-vitro, |
Nor, |
HUVECs |
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angioG↓, BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of
VEGF↓,
TumVol↓, BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively.
Apoptosis↑, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions.
HSP60/HSPD1↓,
HTRA↓,
survivin↓,
XIAP↓,
P21↑,
*toxicity↓, Notably, it is responsible for the spiciness of black pepper, and has been widely used as a safe food flavoring additive with official approval from the Food and Drug Administration
*neuroP↑, BCP was reported to exert a neuroprotective effect in human neuroblastoma SH-SY5Y cells
*ROS↓, intraperitoneally injected BCP at the dose of 50 mg/kg for one month has successfully attenuated oxidative stress, inhibited inflammatory mediator cyclooxygenase-2 and reduced neuroinflammation
*COX2/PTGS2↓,
*Inflam↓,
*cardioP↑, BCP has been recently shown to exert a remarkable cardioprotective effect against doxorubicin-induced acute cardiotoxicity in albino Wistar rats
AntiCan↑, in vitro studies have suggested that BCP exerts significant anti-cancer effects against different types of cancer cell lines.
ChemoSen↑, BCP potentiated the anti-cancer activity of paclitaxel on human colorectal adenocarcinoma (DLD-1), human breast cancer (MCF-7), and murine fibroblast (L-929) cells.
ROS↑, reported to induce apoptosis of human epidermoid skin cancer cells, mediated by production of reactive oxygen species with loss of mitochondrial membrane potential, as well as alteration of specific apoptotic markers like an increase in Bax/Bcl-2 rat
MMP↑,
Bax:Bcl2↑,
TumCG↓, BCP Inhibited Tumor Growth in an HCT-116 Cells Transplanted Mouse Xenograft Model
*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2/PTGS2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju
| - |
in-vitro, |
CRC, |
NA |
|
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- |
in-vivo, |
NA, |
NA |
|
|
|
5LO↓, boswellic acids, is known to be a non-redox and non-competitive inhibitor of 5-lipoxygenase
TumCG↓,
Let-7↑,
miR-200b↑, AKBA significantly up-regulated expression of the let-7 and miR-200 families in various CRC cell lines
NF-kB↓,
cMyc↓,
cycD1/CCND1↓,
MMP9↓,
CXCR4↓,
VEGF↓,
Bcl-xL↓,
survivin↓,
IAP1↓,
XIAP↓,
TumCG↓,
CDK6↓,
Vim↓,
E-cadherin↑,
| - |
Review, |
Var, |
NA |
|
|
|
- |
Review, |
Park, |
NA |
|
|
|
- |
Review, |
AD, |
NA |
|
|
|
AntiCan↑, Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial.
*neuroP↑,
*cardioP↑,
*AntiBio↑,
*BioAv↑, Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant wit
*toxicity↓,
*BioAv↑, integrated in many cosmetic formulations due to its skin soothing effects, well documented dermal absorption
*motorD↑, improvement in locomotor activity, a reduction in the expression of thiol and a reinstate of the activity of mitochondrial complex-I.
*SOD↑, α-Bisabolol also increased the mRNA level of antioxidants proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product.
*Catalase↑,
*Keap1↑,
*MDA↓, α-Bisabolol attenuated oxidative insult by reducing malondialdehyde (MDA), restoring depleted glutathione (GSH) and improving SOD and CAT activity.
*GSH↑,
*IL1β↓, attenuated neuroinflammation by reducing glial cells activation and subsequent release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and mediators (iNOS and COX-2).
*IL6↓,
*TNF-α↓,
*iNOS↓,
*COX2/PTGS2↓,
*lipid-P↓, α-Bisabolol restored mitochondrial function by preventing mitochondrial lipid peroxidation, cytochrome-C release and most importantly preserving Complex-I activity
*Cyt‑c↓,
*ROS↓, The study concluded that α-Bisabolol safeguarded against the induced upsurge of ROS and nitrite.
*MMP↑, α-Bisabolol treatment also restored mitochondrial membrane potential (MMP) validating its antioxidant effect.
*antiOx↑,
*AChE↓, showed a significant reduction in AChE activity and an ability to avert Ach depletion.
*Apoptosis↓, α-Bisabolol protected cells from Aβ triggered apoptosis by reducing Bax and Caspase-3 and increasing Bcl-2 activity.
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BACE/β-secretase↓, α-Bisabolol inhibitory activity on BACE1 and found a decrease in BACE1 activity following α-Bisabolol treatment
*BChE↓, AChE, BuChE, β-secretase actions were decreased significantly in cells pretreated with α-Bisabolol
*eff↑, The compound clearly illustrated a potent anti-AchE activity of 95.869% similar to the activity of donepezil, a standard drug. I
*Aβ↓, The compound also disaggregated Aβ25–35 peptide and protected against its induced toxicity by increasing neuro2a cells viability [
*ATP↑, figure 2
RadioS↑, α-Bisabolol and Anticancer Effects, figure 3
Cyt‑c↑,
Casp3↑,
Casp8↑,
Casp9↑,
Apoptosis↑,
PARP↑,
BAX↑,
BID↑,
NF-kB↑,
Fas↑,
EGFR↑,
TIMP2↑,
XIAP↓,
COX2/PTGS2↓,
Bak↓,
Bcl-2↓,
P53↑, The expression of p53 (a transcription factors whose products might lead to apoptosis), NF-κB and Fas was increased following α-Bisabolol treatment, indicating their function in mediating α-Bisabolol-induced apoptosis in the cancer cell line.
HER2/EBBR2↓,
FGF↓,
CEA↓,
Akt↓,
TumCCA↑, α-Bisabolol suppresses the cellular proliferation at G2/M cell cycle phase.
*Imm↑, reported that α-Bisabolol boosted the immunity response by T-cell subsets (CD4 and CD8) supplementation in treated mice.
*CD4+↑,
*CD8+↑,
*BBB↑, ↑ BBB penetration
*Pain↓, α-Bisabolol based mouthwash to that of chlorhexidine in reducing pain during brushing
*cardioP↑, α-Bisabolol and Cardioprotection, figure 5
*TBARS↓, rats co-treated with α-Bisabolol showed reduced LOOH and TBARS and increased SOD, CAT and GSH.
*SOD↑,
*Catalase↑,
*GSH↑,
*AntiBio↑, α-Bisabolol demonstrated an antibacterial effect against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa as well as a synergism against S. aureus, when combined with the antibiotic norfloxacin and against E. coli when combined with
*AntiFungal↑, ↓ fungal growth
*GastroP↑, α-Bisabolol and Gastroprotection. oral administration of α-Bisabolol was realized to attenuate gastric damage and to provide cytoprotection in stomach.
*RenoP↑, The nephroprotective effects of α-Bisabolol and the underlying mechanisms are summarized in Table 10.
*creat↓, ↓ creatinine, urea, uric acid
*uricA↓,
*Inflam↓, Anti-Inflammatory Effects of α-Bisabolol
*iNOS↓, ↓ iNOS, COX-2, TNF-α, p65 PGE2, nitrite, IL-6, ↓ MMP13
*COX2/PTGS2↓,
*TNF-α↓,
*IL6↑,
*MMP13↓,
MMP↓, Mechanistically, the CAPE-mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase-9.
Casp3↑,
survivin↓, CAPE also modulated survivin and X-linked inhibitor of apoptosis,
XIAP↓, survivin and XIAP were investigated to determine the exact mechanism underlying CAPE-mediated apoptosis. As expected, CAPE administration resulted in the downregulation of both proteins
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in-vitro, |
Melanoma, |
U266 |
|
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- |
in-vitro, |
Melanoma, |
RPMI-8226 |
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TumCP↓, Celastrol inhibited the proliferation of MM cell lines regardless of whether they were sensitive or resistant to bortezomib and other conventional chemotherapeutic drugs.
ChemoSen↑, It also synergistically enhanced the apoptotic effects of thalidomide and bortezomib.
cycD1/CCND1↓, down-regulation of various proliferative and anti-apoptotic gene products including cyclin D1, Bcl-2, Bcl-xL, survivin, XIAP and Mcl-1.
Bcl-2↓,
survivin↓, Bcl-2, Bcl-xL, XIAP and survivin (BIRC5) were decreased with Hsp90 inhibition
XIAP↓,
Mcl-1↓,
NF-kB↓, suppression of constitutively active NF-κB
IL6↓, Celastrol also inhibited both the constitutive and IL6-induced activation of STAT3
STAT3↓,
Apoptosis↑, which induced apoptosis as indicated by an increase in the accumulation of cells in the sub-G1 phase, an increase in the expression of pro-apoptotic proteins and activation of caspase-3
TumCCA↑,
Casp3↑,
HSP90↓, Predictive analysis of HSP90 activity knock-down along with HO-1 induction
HO-1↑,
JAK2↓, Active phosphorylated STAT3, JAK2 and Src were all show reduced
Src↓,
Akt↑, Celastrol suppresses Akt activation and inhibits the expression of anti-apoptotic proteins in MM cells
TumCG↓, . Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related
TumCP↓,
Apoptosis↑, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration.
TumCCA↑,
angioG↓,
TumCI↓,
TumCMig↓,
SUV39H↓, chaetocin inhibits the activities of histone lysine methyltransferase SUV39H1
TrxR↓, formed covalent adducts with numerous proteins, including the thioredoxin-thioredoxin reductase (Trx-TrxR) system, hypoxia inducible factor-1 alpha (HIF-1α), heat shock protein 90 (Hsp90)
Hif1a↓,
HSP90↓,
ox-Trx1↑, ↑ oxidized TRX-1 & ROS activation; ↓ PI3K/AKT pathway & p-AKT; ↑ caspase-3, caspase-8 & caspase-9 activation; ↑ cleaved PARP proteins; ↓ BCL-2, BCL-XL, MCL-1, XIAP
ROS↑,
PI3K↓,
Akt↓,
Casp3↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
XIAP↓,
DR5↑, ↑ DR5 & CHOP, ATF3;
CHOP/DDIT3↑,
ATF3↑,
angioG↓, chaetocin also indirectly targets tumour cells by inducing antiangiogenic effects in the tumour microvasculature.
VEGF↑, robust decrease in secreted VEGF in the culture media of treated cells and subsequent downregulation of the target genes of VEGFA, LDHA, ENO1 and HZF-1,
LDHA↓,
ENO1↓,
| - |
vitro+vivo, |
GC, |
HGC27 |
|
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- |
in-vitro, |
GC, |
AGS |
|
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- |
in-vitro, |
GC, |
BGC-823 |
|
|
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- |
in-vitro, |
GC, |
SGC-7901 |
|
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- |
in-vitro, |
Nor, |
HEK293 |
|
|
|
TumCP↓, In this study, we showed that chaetocin, a natural product isolated from the Chaetomium species of fungi, inhibited proliferation, induced G 2/M phase arrest and caspase-dependent apoptosis in both in vitro and in vivo models
TumCCA↑,
Casp↑,
Apoptosis↑,
TrxR1↓, Chaetocin inactivated TRXR-1, resulting in the accumulation of reactive oxygen species (ROS) in GC cells;
ROS↑, results suggest that chaetocin induces ROS production by inhibiting the TRX-TRXR system and
that this ROS production is required for chaetocin-mediated apoptosis in GC cells.
eff↓, cotreatment of GC cells with the ROS scavenger N-acetyl-L-cysteine (NAC) attenuated chaetocin-induced apoptosis
eff↑, chaetocin-induced apoptosis was significantly increased when GC cells were cotreated with auranofin.
PI3K↓, chaetocin was shown to inactivate the PI3K/AKT pathway by inducing ROS generation;
Akt↓,
TumCG↓, Chaetocin inhibits the growth of GC cells
cl‑PARP↑, chaetocin-induced PARP cleavage (an indicator of apoptosis) in HGC-27 and AGS cells.
cl‑Casp3↑, increased the cleaved forms of caspase-3, −9, and −8 in HGC-27 and AGS cells, illustrating that chaetocin may induce caspase-dependent apoptosis of GC cells
cl‑Casp9↑,
cl‑Casp8↑,
Bcl-2↓, antiapoptotic proteins BCL-2, BCL-XL, MCL-1, XIAP and survivin decreased following chaetocin treatment
Bcl-xL↓,
Mcl-1↓,
XIAP↓,
survivin↓,
TumVol↓, chaetocin effectively reduced the volume and weight of HGC-27 xenograft tumors
TumW↓,
Weight∅, and no significant losses were detected in the body weights of the experimental animals
toxicity↓, chaetocin significantly restrains the growth of GC cell xenografts but has no major side effects in mice
Ki-67↓, ki-67, a biomarker related to proliferation, was downregulated in response to chaetocin
other↝, However, the TRX-TRXR system has recently been found to be upregulated in a variety of human cancers including gastric, colorectal, lung and liver cancers, and overexpression of specific components of this system is linked to tumor cell prof
*antiOx↑, antioxidant (13), anti-inflammatory (14), antibacterial (15), anti-hypertensive (16), anti-allergic (17), vasodilator (18),
Inflam↓,
*hepatoP↑, anti-diabetic (19), anti-anxiety (10), anti-viral (20), anti-estrogen (21), liver protective (22), anti-aging (23), anti-seizure (24), and anti-cancer effects (25)
AntiCan↑,
Cyt‑c↑, (1) facilitating the release of cytochrome C from the mitochondria,
Casp3↑, (2) activating caspase-3 and inhibiting the activity of the XIAP molecule,
XIAP↓,
p‑Akt↓, (3) reducing AKT phosphorylation and triggering the PI3K pathway and induction of apoptosis
PI3K↑,
Apoptosis↑,
COX2/PTGS2↓, chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2.
FAK↓, ESCC cells: resultant blockage of the FAK/AKT signaling pathways
AMPK↑, A549: activation of AMPK by chrysin contributes to Akt suppression
STAT3↑, 4T1cell: inhibited STAT3 activation
MMP↓, Chrysin induces apoptosis through the intrinsic mitochondrial pathway that disrupts mitochondrial membrane potential (MMP) and increases DNA fragmentation.
DNAdam↑,
BAX↑, produces pro-apoptotic proteins, including Bax and Bak, and activates caspase-9 and caspase-3 in various cancer cells
Bak↑,
Casp9↑,
p38↑, chrysin can inhibit tumor growth by activating P38 MAPK and stopping the cell cycle
MAPK↑,
TumCCA↑,
ChemoSen↑, beneficial in inhibiting chemotherapy resistance of cancer cells
HDAC8↓, chrysin suppresses tumorigenesis by inhibiting histone deacetylase 8 (HDAC8)
Wnt↓, chrysin can attenuate Wnt and NF-κB signaling pathways
NF-kB↓,
angioG↓, chrysin can inhibit angiogenesis and inducing apoptosis in HTh7 cells, 4T1 mice, and MDA-MB-231 cells
BioAv↓, low bioavailability of flavonoids such as chrysin
TumCP↓, chrysin has shown to inhibit proliferation and induce apoptosis, and is more potent than other tested flavonoids in leukemia cells
Apoptosis↑,
Casp↑, chrysin is likely to act via activation of caspases and inactivation of Akt signaling in the cells.
PCNA↓, inhibited the growth of cervical cancer cells, HeLa, via apoptosis induction and down-regulated the proliferating cell nuclear antigen (PCNA) in the cells.
p38↑, chrysin potentially induced p38, therefore activated NFkappaB/p65 in the HeLa cells
NF-kB↑,
DNAdam↑, only apigenin, chrysin, quercetin, galangin, luteolin and fisetin were found to clearly induce the oligonucleosomal DNA fragmentation at 50 μM after 6 h of treatment
XIAP↓, down-regulation of X-linked inhibitor of apoptosis protein (XIAP) in the U937 cells
Cyt‑c↑, (1) chrysin mediated the release of cytochrome c from mitochondria into the cytoplasm;
Casp3↑, (2) chrysin induced elevated caspase-3 activity and proteolytic cleavage of its downstream targets, such as phospholipase C-gamma-1 (PLC-gamma1), which is correlated with down-regulation of XIAP;
Akt↓, (3) chrysin decreased phosphorylated Akt levels in cells where the PI3K pathway plays a role in regulating the mechanism.
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling by inhibiting the PI3K pathway
hTERT/TERT↓, A significant decrease in human telomerase reverse transcriptase (hTERT) expression levels was also observed in leukemia cells treated with 60 ng/mL Manisa propolis, owing to its constituent of chrysin
COX2/PTGS2↓, Chrysin also inhibited the lipopolysaccharide-induced COX-2 expression via inhibition of nuclear factor IL-6 (NF-IL6)
*Inflam↓, anti-inflammatory [21] and anti-oxidant effects [22], and has shown cancer chemopreventive activity via induction of apoptosis in diverse range of human and rat cell types.
*antiOx↑,
*chemoPv↑,
AR-V7?,
CYP19?, Chrysin has recently shown to be a potent inhibitor of aromatase [18] and of human immunodeficiency virus activation in models of latent infection
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2/PTGS2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2/PTGS2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,
Apoptosis↑, chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells
TumCCA↑,
angioG↓,
TumCI↓,
TumMeta↑,
*toxicity↓,
selectivity↑,
chemoPv↑, Induction of phase II detoxification enzymes, such as glutathione S-transferase (GST) or NAD(P)H:quinone oxidoreductase (QR) is one of the major mechanism of protection against initiation of carcinogenesis
*GSTs↑,
*NADPH↑,
*GSH↑, upregulation of antioxidant and carcinogen detoxification enzymes (glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), GST and QR)
HDAC8↓, inhibits of HDAC8 enzymatic activity
Hif1a↓, Prostate DU145: Inhibits HIF-1a expression through Akt signaling and abrogation of VEGF expression
*ROS↓, chrysin (20 and 40 mg/kg) was shown to exhibit chemopreventive activity by ameliorating oxidative stress and
inflammation via NF-kB pathway
*NF-kB↓,
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling in human myeloid leukemia cells by preventing the PI3 K pathway
cl‑PARP↑, (PARP) and caspase-3 and concurrently decreasing pro-survival proteins survivin and XIAP
survivin↓,
XIAP↓,
Casp3↑, activation of caspase-3 and -9.
Casp9↑,
GSH↓, chrysin sustains a significant depletion of intracellular GSH concentrations in human NSCLC cells
ChemoSen↑, chrysin potentiates cisplatin toxicity, in part, via synergizing pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and by depleting cellular GSH, an important antioxidant defense
Fenton↑, ability to participate in a fenton type chemical reaction
P21↑, upregulation of p21 independent of p53 status and decrease in cyclin D1, CDK2 protein levels
P53↑,
cycD1/CCND1↓,
CDK2↓,
STAT3↓, chrysin inhibits angiogenesis through inhibition of STAT3 and VEGF release mediated by hypoxia through Akt signaling pathway
VEGF↓,
Akt↓,
NRF2↓, Chrysin treatment significantly reduced
nrf2 expression in cells at both the mRNA and protein levels
through down-regulation of PI3K-Akt and ERK pathways.
Dose↝, Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications.
TumCP↓, CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis.
TumCCA↑,
Apoptosis↑,
TumCMig↓,
TumCI↓,
angioG↓,
*Inflam↓, including anti-inflammatory (3), antioxidant (4), antiviral (5), anti-bacterial (6), antithrombic (7), hypoglycemic (8), hepatoprotective (9), anti-diabetic (10), neuroprotective (11) and anticancer effects
*antiOx↑,
*Bacteria↓,
*AntiThr↑,
*hepatoP↑,
*AntiDiabetic↑,
*neuroP↑,
AntiCan↑,
ChemoSen↑, can enhance the effectiveness of anticancer drugs and ensure patient safety.
*BioAv↝, the bioavailability of intravenous administration of CA was superior to that of oral administration
*BioAv↑, A into CA solid lipid nanoparticles, which increased the oral bioavailability of CA by >1.69 times.
eff↑, Especially when combined with hyperthermia therapy at 42°C and 43°C, CA could inhibit cell proliferation
CDK1↓, CB403 (Fig. 1) is a cinnamaldehyde derivative that inhibits the activity of cyclin-dependent kinases (CDKs), particularly CDK1, CDK2 and CDK4, thereby halting cell cycle progression.
CDK2↓,
CDK4↓,
cJun↓, 2-hydroxycinnamaldehyde (HCA; Fig. 1) inhibits the growth of SW620 colon cancer cells by reducing the expression of c-Jun and c-Fos, inhibiting the DNA binding activity of activator protein 1, and inducing cell apoptosis
cFos↓,
Apoptosis↑,
PI3K↓, CA can induce apoptosis in colon cancer cells by inhibiting the PI3K/Akt signaling pathway
Akt↓,
E-cadherin↑, CA upregulates the expression of E-cadherin while downregulating the expression of matrix metalloproteinase-2 (MMP2) and MMP9
MMP2↓,
MMP9↓,
TOP1↓, increases the sensitivity of CRC cells to 5-FU by reducing the expression of thymidylate synthase, ERCC1, DNA topoisomerase 1 and BRCA1
BRCA1↓,
ROS↑, CA was also able to induce apoptosis in cancer cells by increasing intracellular ROS levels
BAX↑, A induces cell apoptosis by upregulating Bax expression, and downregulating Bcl-2 and X-linked inhibitor of apoptosis (XIAP) expression
Bcl-2↓,
XIAP↓,
MMP↓, CA can also induce apoptosis in leukemia K562 cells by reducing the mitochondrial transmembrane potential via mitochondrial-mediated pathways
STAT3↓, figure 2
mTOR↓,
NF-kB↓, ↓NF-κB
eff↑, CA-Cu-PDA was able to release copper ions and CA in tumor cells, and weakened the antioxidant system by binding to glutathione (GSH), which in turn produced additional ROS, thereby inducing enhanced oxidative stress effects
toxicity↓, Consistent with these findings, another study has demonstrated that CA does not exhibit genotoxic or carcinogenic effects on the body
cardioP↑, CA has demonstrated a capacity to alleviate cardiotoxicity induced by DOX
TumCG↓, inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins.
Apoptosis↑,
TumCCA↑,
TumMeta↓,
angioG↓,
chemoPv↑,
BioAv↓, CuB has been studied to be ~10% with plasma concentration ranging from 4.85 to 7.81 μg/L after 30 mins of oral dosing.
Half-Life↝, Studies have shown that they reach highest plasma concentration within 1.75 h and an elimination half-life of ~2.5 h.
cycD1/CCND1↓, decreased Cyclin D1 and Cyclin E1 levels.
cycE/CCNE↓,
Casp3↑, CRC cell lines underwent in vitro cell death when exposed to CuB, which was accompanied by caspase-3 and cleaved PARP
cl‑PARP↑,
JNK↑, (TNBC), cucurbitacin E strongly boosted JNK activation while considerably decreasing AKT and ERK activation in MDA-MB-468 cells.
Akt↓,
ERK↓,
survivin↓, also significantly decreased expression of Cyclin D1, Survivin, XIAP, Bcl2 and Mcl-1
XIAP↓,
Bcl-2↓,
Mcl-1↓,
ROS↑, In the pancreatic cancer cell line Capan-1, CuD induced cell-cycle arrest and death via the ROS/p38 pathway [43
NRF2↓, Recent studies have shown that CuIIb and cucurbitacin B induced apoptosis in cervical cancer cell lines by Nrf2 inhibition,
FAK↓, It successfully inhibited angiogenesis by targeting the FAK/MMP-9 signaling axis
MMP9↓,
VEGF↓, suppressed angiogenesis by downregulating the expression of HIF-1 targets, VEGF, VEGFR2 phosphorylation and erythropoietin
VEGFR2/KDR/Flk1↓,
*NF-kB↓, Dietary cucurbitacin E has been shown to reduce inflammation and immunosuppression by downregulating the NF-κB signaling pathway
TLR4↝, Cucurbitacin B was observed to directly bind to toll-like receptor 4 (TLR4) and activate NLRP3 inflammasome, which further ultimately executed pyroptosis in A549 cells.
NLRP3↑,
Pyro↑,
GSH↓, It was observed that treatment with CuI and doxorubicin decreased glutathione (GSH) levels, enhancing cytotoxicity in tumors.
*antiOx↑, Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators
*Inflam↑,
*ROS↓,
Apoptosis↑, Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers
TumCP↓,
BioAv↓, application is limited by its poor bioavailability due to its rapid metabolism and low absorption.
Half-Life↓,
eff↑, curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy.
TumCCA↑, Studies have demonstrated that curcumin can suppress the proliferation of cancer cells by interfering with the cell cycle [21,22]
BAX↑, Curcumin enhances the expression of pro-apoptotic proteins such as Bax, Bak, PUMA, Bim, and Noxa and death receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5
Bak↑,
PUMA↑,
BIM↑,
NOXA↑,
TRAIL↑,
Bcl-2↓, curcumin decreases the levels of anti-apoptotic proteins like Bcl-2, Bcl-XL, survin, and XIAP
Bcl-xL↓,
survivin↓,
XIAP↓,
cMyc↓, This shift in the balance of apoptotic regulators facilitates the release of cytochrome c from mitochondria [33,35] and activates caspases
Casp↑,
NF-kB↓, Curcumin suppresses the activity of key transcription factors like NF-κB, STAT3, and AP-1 and interferes with critical signal transduction pathways such as PI3K/Akt/mTOR and MAPK/ERK.
STAT3↓,
AP-1↓,
angioG↓, curcumin inhibits angiogenesis and metastasis by downregulating VEGF, VEGFR2, and matrix metalloproteinases (MMPs).
TumMeta↑,
VEGF↓,
MMPs↓,
DNMTs↓, Epigenetic modifications through the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) further contribute to its anticancer properties.
HDAC↓,
ROS↑, curcumin-loaded nanoparticles showed significant cytotoxicity in the SCC25, MDA-MB-231, and A549 cell lines, with a decrease in tumor cell proliferation, an increase in ROS, and an increase in apoptosis.
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Var, |
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AD, |
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*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,
Apoptosis↑,
cl‑Casp3↑,
miR-340↑,
cl‑PARP↑,
XIAP↓,
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2/PTGS2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage
AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2/KDR/Flk1↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP/DDIT3↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity
Telomerase↓, EGCG stimulates telomere fragmentation through inhibiting telomerase activity.
DNMTs↓, EGCG reduced DNMTs,
cycD1/CCND1↓, EGCG also reduced the protein expression of cyclin D1, cyclin E, CDK2, CDK4, and CDK6. EGCG also inhibited the activity of CDK2 and CDK4, and caused Rb hypophosphorylation
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
HATs↓, EGCG can inhibit certain biomedically important molecular targets such as DNMTs, HATs, and HDACs
HDAC↓,
selectivity↑, EGCG has shown higher cytotoxicity in cancer cells than in their normal counterparts.
uPA↓, EGCG blocks urokinase, an enzyme which is essential for cancer growth and metastasis
NF-kB↓, EGCG inhibits NFκB and expression of TNF-α, reduces cancer promotion
TNF-α↓,
*ROS↓, It acts as strong ROS scavenger and antioxidant,
*antiOx↑,
Hif1a↓, ↓ HIF-1α; ↓ VEGF; ↓ VEGFR1;
VEGF↓,
MMP2↓, ↓ MMP-2; ↓ MMP-9; ↓ FAK;
MMP9↓,
FAK↓,
TIMP2↑, TIMP-2; ↑
Mcl-1↓, ↓ Mcl-1; ↓ survivin; ↓ XIAP
survivin↓,
XIAP↓,
PCNA↓, ↓ PCNA; ↑ 16; ↑ p18; ↑ p21; ↑ p27; ↑ pRb; ↑ p53; ↑ mdm2
p16↑,
P21↑,
p27/CDKN1B↑,
pRB↑,
P53↑,
MDM2↑,
ROS↑, ↑ ROS; ↑ caspase-3; ↑ caspase-8; ↑ caspase-9; ↑ cytochrome c; ↑ Smac/DIABLO; ↓↑ Bax; Z Bak; ↓ cleaved PPAR;
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑,
Diablo↑,
BAX⇅,
cl‑PPARα↓,
PDGF↓, ↓ PDGF; ↓ PDGFRb; ↓ EGFR;
EGFR↓,
FOXO↑, activated FOXO transcription factors
AP-1↓, The inhibition of AP-1 activity by EGCG was associated with inhibition of JNK activation but not ERK activation.
JNK↓,
COX2/PTGS2↓, EGCG reduces the activity of COX-2 following interleukin-1A stimulation of human chondrocytes
angioG↓, EGCG inhibits angiogenesis by enhancing FOXO transcriptional activity
CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,
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PC, |
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PC, |
CD44+ |
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PC, |
CD24+ |
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PC, |
ESA+ |
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HH↓, EGCG also inhibited the components of Shh pathway (smoothened, patched, Gli1 and Gli2)
Smo↓,
PTCH1↓,
PTCH2↓,
Gli1↓,
GLI2↓,
Gli↓,
Bcl-2↓, inhibiting the expression of Bcl-2 and XIAP, and activating caspase-3
XIAP↓,
Shh↓,
survivin↓,
Casp3↑,
Casp7↑,
CSCs↓, EGCG inhibited the expression of pluripotency maintaining transcription factors (Nanog, c-Myc and Oct-4), and self-renewal capacity of pancreatic CSCs.
Nanog↓,
cMyc↓,
OCT4↓,
EMT↓, EGCG inhibited EMT by inhibiting the expression of Snail, Slug and ZEB1, and TCF/LEF transcriptional activity,
Snail↓,
Slug↓,
Zeb1↓,
TumCMig↓, significantly reduced CSC’s migration and invasion, suggesting the blockade of signaling involved in early metastasis.
TumCI↓,
eff↑, combination of quercetin with EGCG had synergistic inhibitory effects on self-renewal capacity of CSCs through attenuation of TCF/LEF and Gli activities
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Apoptosis↑,
Nanog↓,
cMyc↓,
OCT4↓,
Snail↓,
Slug↓,
Zeb1↓,
TCF↓,
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HCC, |
Hep3B |
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HCC, |
HUH7 |
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STAT3↓, Emodin suppressed STAT3 activation in a dose- and time-dependent manner in HCC cells
Akt↓, Emodin inhibits IL-6-inducible Akt phosphorylation in HCC cells
cSrc↓, Emodin suppresses constitutive activation of c-Src
JAK1↓, Emodin suppresses constitutive activation of JAK1 and JAK2 in HCC cells
JAK2↓,
SHP1↑, Emodin induces the expression of SHP-1 in HCC cells
cycD1/CCND1↓, Emodin down-regulates the expression of cyclin D1, Bcl-2, Bcl-xL, Mcl-1, survivin and VEGF
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
survivin↓,
VEGF↓,
TumCP↓, Emodin inhibits the proliferation of HCC cells in a dose- and time-dependent manner
Casp3↑, Emodin activates caspase-3 and causes PARP cleavage
cl‑PARP↑,
ChemoSen↑, Emodin potentiates the apoptotic effect of doxorubicin and paclitaxel in HepG2 cells
XIAP↓, The reduction in survival markers like Bcl-2, Bcl-xL, XIAP and survivin was similar for HepG2 cells treated with emodin
Inflam↓, emodin demonstrates anti-neoplastic, anti-inflammatory, anti-angiogenesis, and toxicological potential for use in pharmacology, both in vitro and in vivo
angioG↓,
TumCCA↑, Emodin demonstrates cytotoxic effects (e.g., cell death) through the arrest of the cell cycle and the induction of apoptosis in cancer cells.
Apoptosis↑,
HIF-1↓, As a novel inhibitor of HIF-1, emodin is an adjunct that boosts the efficacy of cytotoxic drugs used for the treatment of prostate cancer DU-145 cells,
TumCI↓, while inhibiting angiogenesis, invasion, migration, chemical-induced carcinogen-DNA adduct formation, HER2/neu, CKII kinase, and p34cdc2 kinase in human cancer cells.
TumCMig↓,
HER2/EBBR2↓,
CK2↓,
ROS↑, In addition, emodin enhances arsenic trioxide-induced apoptosis by generating ROS and inhibiting survival signaling
AR↓, Emodin downregulates androgen receptors and inhibits the cellular growth of prostate cancer
JAK2↓, Emodin selectively inhibits the interleukin–6-induced JAK2/STAT3 pathway and induces apoptosis in myeloma cells via the downregulation of myeloid cell leukemia 1 (Mcl-1) cells
STAT3↓,
Mcl-1↓,
NAT↓, emodin and aloe-emodin inhibit N-acetyltransferase (NAT) activity and gene expression in mouse leukemia L1210 cells
ChemoSen↑, Emodin enhances apoptosis in cisplatin-induced gallbladder carcinomas in a ROS-dependent manner and suppresses survivin expression
survivin↓,
XIAP↓, Emodin downregulates X-linked inhibitor of apoptosis protein (XIAP) expression [84] and inhibits NF-κB against human pancreatic cancer
NF-kB↓,
*neuroP↑, Emodin induces apoptosis in the mouse microglial BV-2 cell line via Tribbles homolog 3 (TRB3) and eliminates inflammatory microglia, thereby exerting neuroprotective effects
*hepatoP↑, Emodin also demonstrates hepatoprotective effects against CCl4-induced liver injury
NF-kB↓, highly potent inhibitor of NF-kappaB activation
TNF-α↓,
COX2/PTGS2↓,
cycD1/CCND1↓,
cMyc↓,
MMP9↓,
ICAM-1↓,
MDR1↓,
XIAP↓,
Bcl-2↓,
Bcl-xL↓,
IAP1↓,
IAP2/BIRC3↓,
cFLIP↓,
Bfl-1↓,
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LNCaP |
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in-vitro, |
Pca, |
PC3 |
|
|
|
Dose↝, The half maximal inhibitory concentration (IC50) dose of FA was found to be 300 μM in PC-3 cells and 500 μM in LNCaP cells.
ATR↑, FA inhibited cell proliferation by increasing the gene expressions of ATR, ATM, CDKN1A, CDKN1B, E2F4, RB1, and TP53
ATM↑,
P21↑,
p27/CDKN1B↑,
E2F4↑,
RB1↑,
TP53↑,
cycD1/CCND1↓, and decreasing the gene expressions of CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 in PC-3 cells.
CDK2↓,
CDK4↓,
CDK6↓,
TumCP↓, suppressed cell proliferation by increasing in the gene expressions of CASP1, CASP2, CASP8, CYCS, FAS, FASLG, and TRADD
Casp1↑,
Casp2↑,
Casp8↑,
Fas↑,
TRADD↑,
Bcl-2↓, and decreasing in the gene expressions of BCL2 and XIAP in LNCaP cells
XIAP↓,
TumCCA↑, FA may lead to cell cycle arrest in PC-3 cells while it may cause apoptosis in LNCaP cells.
TumCP↓, Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage
TumCI↓,
TumCCA↑,
TumCG↓,
Apoptosis↑,
cl‑PARP↑,
PKCδ↓, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin
ROS↓,
ERK↓,
NF-kB↓,
survivin↓,
ROS↑, In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis
PI3K↓, Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)
Akt↓,
mTOR↓,
MAPK↓, phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively,
p38↓,
HER2/EBBR2↓, (HER2)/neu‐overexpressing breast cancer cell lines. Fisetin caused induction through inactivating the receptor, inducing the degradation of the proteasomes, reducing its half‐life
EMT↓, In addition, mutation of epithelial‐to‐mesenchymal transition (EMT)
PTEN↑, up‐regulation of expression of PTEN mRNA and protein were reported after fisetin treatment
HO-1↑, In breast cancer cells (4T1 and JC cells), fisetin increased HO‐1 mRNA and protein expressions, elevated Nrf2 expression
NRF2↑,
MMP2↓, fisetin reduced MMP‐2 and MMP‐9 enzyme activity and gene expression for both mRNA levels and protein
MMP9↓,
MMP↓, fisetin treatment further led to permeabilization of mitochondrial membrane, activation of caspase‐8 and caspase‐9, as well as the cleavage of poly(ADP‐ribose) polymerase 1
Casp8↑,
Casp9↑,
TRAILR↑, enhanced the levels of TRAIL‐R1
Cyt‑c↑, mitochondrial releasing of cytochrome c into cytosol, up‐regulation and down‐regulation of X‐linked inhibitor of apoptosis protein
XIAP↓,
P53↑, fisetin also enhanced the protein p53 levels
CDK2↓, lowered cell number, the activities of CDK‐2,4)
CDK4↓,
CDC25↓, it also decreased cell division cycle protein levels (CDC)2 and CDC25C, and CDC2 activity (Lu et al., 2005)
CDC2↓,
VEGF↓, down‐regulating the expressions of p‐ERK1/2, vascular endothelial growth factor receptor 1(VEGFR1), p38, and pJNK, respectively
DNAdam↑, Fisetin (80 microM) showed dose‐dependently caused DNA fragmentation, induced cellular swelling and apoptotic death, and showed characteristics of apoptosis.
TET1↓, lowered the TET1 expression levels
CHOP/DDIT3↑, caused up‐regulation of (C/EBP) homologous protein (CHOP) expression and reactive oxygen species production,
CD44↓, down‐regulation of CD44 and CD133 markers
CD133↓,
uPA↓, down‐regulation of levels of matrix metalloproteinase‐2 (MMP‐2), urokinase‐type plasminogen activator (uPA),
CSCs↓, Being a potent anticancer agent, fisetin administration in in vitro and in vivo studies in kidney renal stem cells (HuRCSCs) effectively inhibited cancer cell stages such as proliferation,
*chemoPv↑, Fisetin has been reported as a chemopreventive/chemotherapeutic agent in several types of cancer and also as a neuroprotective agent.
*neuroP↑,
*antiOx↑, Several studies indicate that fisetin is a promising novel antioxidant. The trolox-equivalent activity concentration (TEAC) value of fisetin has been reported to be 2.80±0.06 (
*GSH↑, Fisetin has been shown to increase intracellular glutathione (GSH) levels in the mouse hippocampal HT-22 cells both in the presence and absence of glutamate
*HO-1↑, the effect of fisetin on the upregulation of heme oxygenase-1 (HO-1)
*NRF2↑, Treatment with fisetin caused increased Nrf2 nuclear translocation and activity.
angioG↓, fisetin may reduce angiogenesis and consequently suppress tumor growth through inhibition of urokinase plasminogen activator (uPA)
TumCG↓,
uPA↓,
MMP1↓, fisetin to be a potent inhibitor of the matrix metalloproteinase (MMP)-1 activity
tumCV↓, Lung Decreased cancer cell viability and clonogenecity, increased PTEN, decreased PI3-K and Akt phosphorylation, activated TSC and AMPK, decreased phosphorylation and activation of mTOR,
PTEN↑,
PI3K↓, Fisetin also acts as a dual inhibitor of PI3K/Akt and mTOR signaling in prostate cancer cells
p‑Akt↓,
AMPK↑,
mTOR↓,
EGFR↓, Inhibited EGFR and NF-κB, decreased COX2 and PGE2, inhibited Wnt/β-catenin signaling, downregulated TCF-4, decreased cyclin D1 and MMP-7
NF-kB↓,
COX2/PTGS2↓,
PGE2↓,
Wnt↓,
β-catenin/ZEB1↓,
TCF↓,
cycD1/CCND1↓,
MMP7↓,
RadioS↑, Enhanced radiosensitivity of p53-mutant colon cancer cells, augmented radiation-induced G2/M arrest and apoptosis
PSA↓, Prostate Slowed tumor growth, decreased serum PSA levels
Securin↓, Moreover, fisetin inhibited securin expression regardless of p53 status,
TumCCA↑, accompanied by arrest of cells in the G0/G1 phase of the cell cycle
XIAP↓, fisetin treatment resulted in a decrease in the activity of NF-κB/p65, MMP-9, and X-linked inhibitor of apoptosis (XIAP)
*ERK↑, fisetin was the most effective flavonoid that induced neurite outgrowth by inducing ERK1/2 activation
*p‑CREB↑, Fisetin activated ERK1/2 and induced cAMP-response element-binding protein (CREB) phosphorylation in rat hippocampal slices and enhanced object recognition in mice.
*memory↑,
*GSH↑, It acts as an antioxidant, increases GSH, maintains mitochondrial function in the presence of oxidative stress, has anti-inflammatory activity against microglial cells, and inhibits the activity of 5-lipoxygenase,
*Inflam↓,
*5LO↓,
| - |
in-vitro, |
Pca, |
LNCaP |
|
|
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- |
in-vitro, |
Pca, |
PC3 |
|
|
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- |
in-vitro, |
Pca, |
22Rv1 |
|
|
|
Dose↝, Treatment of fisetin (10–60 μM, 48 h) was found to result in a decrease in the viability of LNCaP, CWR22Rυ1 and PC-3 cells but had only minimal effects on normal prostate epithelial cells
tumCV↓,
selectivity↑,
TumCCA↑, Treatment of LNCaP cells with fisetin also resulted in G1-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↑, activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27.
CDK4↑,
CDK6↑,
P21↑,
p27/CDKN1B↑,
Apoptosis↑, Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage
cl‑PARP↑,
Cyt‑c↑, induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein
XIAP↓,
Casp3↑, significant activation of caspases-3, -8 and -9
Casp8↑,
Casp9↑,
Bcl-2↓, In sharp contrast, the protein expression of Bcl-2 was significantly decreased by fisetin treatment in a dose-dependent fashion
PI3K↓, Inhibition of PI3K and phosphorylation of Akt protein expression by fisetin in LNCaP cells
Akt↓,
AntiCan↑, Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules.
TumCCA↑, Fucoidan treatment results in sub G0/G1 cell accumulation (suggestive of dead cells/apoptotic cells) in a variety of cell types
cycD1/CCND1↓, fucoidan demonstrated significant down regulation of cyclin D1, cyclin D2 and CDK4 in cancer cells
CDK4↓,
MMP↓, ↓ MMP
Casp9↑, Caspase 9 activation
survivin↓, ↓ survivin, cIAP-2
IAP1↓,
Cyt‑c↑, ↑ cytochrome C, Smac/Diablo, Bak, t-Bid
Diablo↑,
Bak↑,
XIAP↓, ↓ XIAP,
VEGF↓, Fucoidan has been found to inhibit the binding of VEGF, a key angiogenesis promoting molecule
angioG↓,
MMP2↓, MMP-2 and MMP-9 playing a major role. Fucoidan attenuates both expression and activity of these enzymes
MMP9↓,
Akt↓, inactivation of AKT by fucoidan
eff↝, The fucoidan structure and monosaccharide composition vary depending on different factors such as the source of fucoidan, the time and location of harvesting and the extraction method, which can affect the fucoidan’s bioactivities.
TumMeta↓, fucoidan induces cell death within tumor cells and increases the survival rate of tumor-bearing animal models by suppression of metastasis and angiogenesis.
*toxicity↓, Sprague–Dawley rats, researchers didn’t observe significant side effects when taking 0–1000 mg/kg fucoidan orally for 28 days.
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
VEGF↓,
angioG↓,
PI3K↓,
Akt↓,
PARP↑,
Bak↑,
BID↑,
Fas↑,
Mcl-1↓,
survivin↓,
XIAP↓,
ERK↓,
EMT↓, Fucoidan can reverse the EMT effectively
EM↑,
IM↓,
Snail↓,
Slug↓,
Twist↓,
TumCP↓, GA directly inhibited proliferation and induced apoptosis in both 5-fluorouracil (5-FU) sensitive and 5-FU resistant colorectal cancer cells; induced apoptosis via activating JNK signaling pathway.
Apoptosis↑,
JNK↑,
TumCCA↑, mechanism of GA-induced cell cycle arrest,
cycD1/CCND1↓, GA decreased the level of cyclin D1 proteins and increased the level of p53, which also confirmed that GA caused G1 arrest in CRC cells.
P53↑,
Casp3↑, active forms of caspases-3, -8 and -9 were increased after GA treatment, matching the pattern of PARP cleavage, demonstrating that GA triggers CRC cell apoptosis via caspase activation.
Casp8↑,
Casp9↑,
cl‑PARP↑,
MMP↓, GA-induced apoptosis is associated with the loss of mitochondrial membrane potential (MMP)
Cyt‑c↑, release of mitochondria proteins such as cytochrome c and AIF from mitochondria to cytosol and/or the nucleus, which are recognized as indicators of the early stage of apoptosis
Bcl-2↓, GA decreased the level of anti-apoptotic proteins Bcl-2, Bcl-xl, Mcl-1, XIAP and survivin in both HCT-15P and HCT-15R cells in a dose- and time-dependent manner.
Bcl-xL↓,
Mcl-1↓,
XIAP↓,
survivin↓,
| - |
in-vitro, |
BC, |
MCF7 |
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- |
in-vitro, |
Nor, |
MCF10 |
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- |
in-vitro, |
CRC, |
HCT116 |
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Casp3↑,
Casp9↑,
Casp8↑,
DR5↑,
survivin↓,
Bcl-2↓,
XIAP↓,
cFLIP↓,
BAX↑,
Cyt‑c↑,
ROS↑, ROS in MCF-7 breast cancer cells, the production of ROS was not observed in non-tumorigenic MCF-10A
GSH↓, Glutathione (GSH) also abolished the garcinol-induced induction of both DR5 and DR4 expression in a dose-dependent manner
*eff↓, Garcinol neither induced the receptors on normal cells, nor sensitized them to TRAIL
| - |
Review, |
Var, |
NA |
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- |
Review, |
IBD, |
NA |
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- |
Review, |
Stroke, |
NA |
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- |
Review, |
Sepsis, |
NA |
|
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|
- |
Review, |
AD, |
NA |
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|
Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.
*AntiCan↑, anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects.
*Bacteria↓,
*AntiViral↑,
*antiD↓,
*RenoP↑, Kidney protection
*hepatoP↑, Liver protection
*eff↑, treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers.
*Sepsis↓,
*AntiArt↑,
*Stroke↓,
TumCMig↓, hyperoside has been shown to inhibit the migration and invasion properties of A549 cells by suppressing the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase-2 inhibitor (TIMP-2), matrix metalloproteinase (MMP)-2
TumCI↓,
MTA1↓,
TIMP2↓,
MMP2↓,
MMP↓, disrupted the penetration of the mitochondrial membrane, and triggered mitochondrial cytochrome C and apoptosis inducers into the cytoplasm
Cyt‑c↑,
Akt↓, inhibited the Akt/mTOR/p70S6K signaling pathway in NSCLC cells to promote autophagy and exerted anticancer activity
mTOR↓,
P70S6K↓,
TumAuto↑,
PD-L1↓, thereby inhibiting PD-L1 expression at the transcriptional leve
TNF-α↓, subsequently, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1b, IL-6 and IL-8, were significantly down-regulated
IL1β↓,
IL6↓,
IL8↓,
Bcl-2↓, Hyperoside was reported to inhibit the over-expression of B-cell lymphoma factor 2 (Bcl)-2 and Bcl-x in lung cancer cells, and up-regulate the preapoptotic factors such as Bax, Bad, and Bak.
Bcl-xL↓,
BAX↑,
BAD↑,
Bak↑,
VEGF↓, decreasing the HeLa cell's vascular endothelial growth factor (VEGF) expression levels in HeLa cells.
Casp3↑, hyperoside promoted apoptosis via enhancing caspase-3 and caspase-8 protein expression, and on the other hand, by promoting tumor suppressor gene P35 expression
Casp8↑,
P53↑,
GSH↓, Hyperoside could also reduce glutathione levels in HeLa cells, superoxide dismutase (SOD), and Catalase (CAT) viability.
SOD↓,
Catalase↓,
TAC↓, reduced the antioxidant capacity and thus to inhibit cancer cell growth
XIAP↓, MCF-7 and 4 T1 cells Decreased the levels of Bcl-2 and XIAP; increased the levels of Bax and cleaved cysteine protease-3; decreased the production of ROS and inhibited NFκB signal pathway
ROS↓,
NF-kB↓,
TLR4↓, MDA-MB-231 cells Inhibited TLR4-NF-κB signaling pathways; decreased the expression of Bcl-2; enhanced the expression of pro-apoptotic Bax and the level of pro-inflammatory cytokine IL-6
P-gp/ABCB1↓, S180 cancer cell Reduced the expression of P-gp, LRP and Bcl-2 and increased the expression of Fas; inhibited bad phosphorylation and increased p27 level
LRP1↓,
Fas↑,
p27/CDKN1B↑,
*cardioP↑, Cardiovascular protection In vivo pulmonary embolism and arterial thrombosis model Prolonged the activated prothrombin time and suppressed thrombin and FXa activities; inhibit the production of PAI-1 induced by TNF-α
*AntiThr↑,
*PAI-1/SERPINE1↓,
*BUN↓, Reduced the contents of serum angiotensin converting enzyme ArgII, ALD, U-mAlb, BUN, SCR, ALT, and AST
*ALAT↓,
*AST↓,
*neuroP?, Neuroprotection
Showing Research Papers: 1 to 50 of 87
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 87
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
CD47↓, 1, E2F4↑, 1, HSP60/HSPD1↓, 2, HTRA↓, 2, miR-124-3p↓, 1, MTA1↓, 1, NAT↓, 1, PFS↑, 1, SUV39H↓, 1, TRADD↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 1, ATF3↑, 1, Catalase↓, 3, Copper↑, 1, Fenton↑, 1, GPx4↓, 1, GSH↓, 7, GSTs↑, 1, HO-1↓, 5, HO-1↑, 3, HO-2↓, 1, ICD↑, 1, lipid-P↓, 1, lipid-P↑, 1, MAD↓, 1, MDA↓, 1, NQO1↑, 1, NRF2↓, 5, NRF2↑, 1, p‑NRF2↓, 1, OXPHOS↓, 1, ROS↓, 2, ROS↑, 23, i-ROS↑, 1, SIRT3↓, 1, SOD↓, 2, SOD↑, 1, TAC↓, 1, ox-Trx1↑, 1, TrxR↓, 2, TrxR1↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
AIF↑, 1, Bfl-1↓, 1, CDC2↓, 1, CDC25↓, 3, MMP↓, 15, MMP↑, 2, OCR↓, 1, PGC-1α↑, 1, XIAP↓, 50,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACSL4↑, 1, ALAT↓, 1, AMPK↑, 4, cMyc↓, 9, ECAR↝, 1, ENO1↓, 1, GlucoseCon↓, 1, Glycolysis↓, 2, HK2↓, 2, lactateProd↓, 1, LDH↓, 2, LDHA↓, 2, LDL↓, 1, PDH↝, 1, PDK1?, 2, PDK1↓, 2, PPARα↓, 1, cl‑PPARα↓, 1, PPARγ↓, 1, SCD1↓, 1, SIRT1↓, 2,
Cell Death(tgid=5) ⓘ
Akt↓, 21, Akt↑, 3, p‑Akt↓, 5, APAF1↑, 1, Apoptosis↑, 30, ASK1↑, 1, BAD↑, 2, Bak↓, 1, Bak↑, 6, BAX↑, 13, BAX⇅, 1, Bax:Bcl2↑, 4, Bcl-2↓, 26, Bcl-xL↓, 14, BID↑, 2, BIM↑, 1, Casp↑, 4, Casp1↑, 1, Casp2↑, 1, Casp3↓, 2, Casp3↑, 23, cl‑Casp3↑, 2, Casp7↑, 3, Casp8↑, 12, cl‑Casp8↑, 1, Casp9↑, 18, cl‑Casp9↑, 1, cFLIP↓, 2, CK2↓, 2, Cyt‑c↓, 1, Cyt‑c↑, 17, Diablo↑, 3, DR4↑, 1, DR5↑, 6, Fas↑, 5, FasL↑, 1, hTERT/TERT↓, 2, IAP1↓, 5, IAP2/BIRC3↓, 2, iNOS↓, 3, JNK↓, 2, JNK↑, 2, MAPK↓, 4, MAPK↑, 1, Mcl-1↓, 12, MDM2↓, 2, MDM2↑, 1, Myc↓, 1, NOXA↑, 2, p27/CDKN1B↑, 5, p38↓, 1, p38↑, 2, Paraptosis↑, 1, PUMA↑, 2, Pyro↑, 1, p‑RSK↑, 1, survivin↓, 32, Telomerase↓, 3, TRAIL↑, 1, TRAILR↑, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
cSrc↓, 1, HER2/EBBR2↓, 3, SOX9?, 1, Sp1/3/4↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
cJun↓, 1, EZH2↓, 2, HATs↓, 1, miR-21↓, 1, miR-27a-3p↓, 1, other↓, 2, other↝, 1, pRB↑, 1, tumCV↓, 4,
Protein Folding & ER Stress(tgid=8) ⓘ
ATF6↑, 1, CHOP/DDIT3↑, 7, p‑eIF2α↑, 2, ER Stress↑, 4, GRP78/BiP↑, 1, HSP27↓, 1, HSP90↓, 3, IRE1↑, 2, PERK↑, 3, UPR↑, 2, XBP-1↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG5↑, 1, Beclin-1↑, 1, LC3A↑, 1, LC3I↑, 1, LC3II↓, 1, LC3II↑, 2, p62↓, 1, TumAuto↑, 4,
DNA Damage & Repair(tgid=10) ⓘ
ATM↑, 2, ATR↑, 1, BRCA1↓, 1, DNAdam↓, 1, DNAdam↑, 9, DNMT1↓, 1, DNMTs↓, 3, p16↑, 2, P53↑, 12, PARP↑, 4, PARP↝, 1, cl‑PARP↑, 13, PCNA↓, 4, SIRT6↓, 1, SIRT6↑, 1, TP53↑, 2, γH2AX↑, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK1↓, 2, CDK2↓, 6, CDK2↑, 2, CDK4↓, 6, CDK4↑, 1, Cyc↓, 1, CycB/CCNB1↓, 1, cycD1/CCND1↓, 17, cycE/CCNE↓, 5, P21↑, 9, RB1↑, 2, p‑RB1↓, 1, Securin↓, 1, TumCCA↑, 22,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
ALDH1A1↓, 1, AR-V7?, 1, CD133↓, 2, CD44↓, 3, CDK8↓, 1, cFos↓, 1, CIP2A↓, 1, CSCs↓, 7, EMT↓, 10, EMT↑, 1, ERK↓, 6, p‑ERK↓, 1, FGF↓, 1, FOXO↑, 2, FOXO3↑, 1, Gli↓, 1, Gli1↓, 2, GSK‐3β↑, 1, p‑GSK‐3β↓, 2, HDAC↓, 4, HDAC8↓, 2, HH↓, 1, Let-7↑, 1, mTOR↓, 7, p‑mTOR↓, 2, Nanog↓, 5, NOTCH↓, 4, NOTCH1↓, 2, NOTCH1↑, 1, OCT4↓, 6, P70S6K↓, 1, PI3K↓, 10, PI3K↑, 1, PTCH1↓, 1, PTCH2↓, 1, PTEN↑, 6, RAS↓, 1, SCF↓, 2, Shh↓, 2, SHP1↑, 1, Smo↓, 2, SOX2↓, 2, Src↓, 1, STAT3↓, 11, STAT3↑, 1, p‑STAT3↓, 2, TCF↓, 2, TOP1↓, 2, TOP2↓, 1, TumCG↓, 10, Wnt↓, 3, Wnt/(β-catenin)↓, 1,
Migration(tgid=13) ⓘ
5LO↓, 1, AP-1↓, 2, Ca+2↑, 3, Ca+2↝, 1, CAFs/TAFs↓, 1, CEA↓, 1, CLDN1↓, 1, CXCL12↓, 1, E-cadherin↑, 7, EM↑, 1, ER-α36↓, 1, FAK↓, 5, p‑FAK↓, 1, Fibronectin↓, 1, GLI2↓, 1, Ki-67↓, 3, LAMs↓, 1, LRP1↓, 1, MALAT1↓, 1, miR-200b↑, 1, miR-340↑, 1, MMP-10↓, 1, MMP1↓, 2, MMP13↓, 1, MMP2↓, 16, MMP3↓, 1, MMP7↓, 1, MMP9↓, 16, MMPs↓, 2, N-cadherin↓, 2, PDGF↓, 1, PKCδ↓, 3, Rho↓, 1, ROCK1↓, 2, Slug↓, 5, SMAD3↓, 1, Snail↓, 9, TET1↓, 1, TET1↑, 1, TGF-β↓, 3, TGF-β↑, 1, TIMP1↓, 1, TIMP2↓, 2, TIMP2↑, 2, TumCI↓, 12, TumCMig↓, 8, TumCP↓, 18, TumMeta↓, 4, TumMeta↑, 2, Twist↓, 4, uPA↓, 5, Vim↓, 8, Zeb1↓, 2, ZO-1↑, 1, α-SMA↓, 1, β-catenin/ZEB1↓, 5,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 19, ATF4↑, 1, EGFR↓, 4, EGFR↑, 1, Endoglin↑, 1, HIF-1↓, 2, Hif1a↓, 10, VEGF↓, 19, VEGF↑, 1, VEGFR2/KDR/Flk1↓, 3, ZBTB10↑, 1,
Barriers & Transport(tgid=15) ⓘ
GLUT1↓, 1, NHE1↓, 1, P-gp/ABCB1↓, 2,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CD4+↓, 1, COX1↓, 1, COX2/PTGS2↓, 12, COX2/PTGS2↑, 1, CXCR4↓, 1, ICAM-1↓, 1, IFN-γ↓, 1, IKKα↓, 1, IL1↓, 1, IL10↓, 1, IL1β↓, 2, IL2↓, 1, IL4↓, 1, IL6↓, 7, IL8↓, 1, Imm↑, 1, Inflam↓, 5, JAK↓, 1, JAK1↓, 1, JAK2↓, 4, MCP1/CCL2↓, 1, NF-kB↓, 22, NF-kB↑, 2, NK cell↑, 1, PD-1↓, 1, PD-L1↓, 3, PD-L1↑, 1, PGE2↓, 4, PSA↓, 1, TLR4↓, 2, TLR4↝, 1, TNF-α↓, 6,
Cellular Microenvironment(tgid=17) ⓘ
IM↓, 1,
Protein Aggregation(tgid=19) ⓘ
NLRP3↑, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
AR↓, 1, CDK6↓, 6, CDK6↑, 2, CYP19?, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 6, BioAv↑, 4, ChemoSen↑, 17, Dose?, 1, Dose↝, 10, Dose∅, 2, eff↓, 3, eff↑, 24, eff↝, 2, Half-Life↓, 1, Half-Life↝, 1, MDR1↓, 1, RadioS↑, 7, selectivity↑, 10,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 1, ALP↓, 1, AR↓, 1, BG↓, 1, BRCA1↓, 1, CEA↓, 1, EGFR↓, 4, EGFR↑, 1, EZH2↓, 2, HER2/EBBR2↓, 3, hTERT/TERT↓, 2, IL6↓, 7, Ki-67↓, 3, LDH↓, 2, Myc↓, 1, PD-L1↓, 3, PD-L1↑, 1, PSA↓, 1, TP53↑, 2,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 7, AntiTum↑, 1, cardioP↑, 2, chemoP↑, 2, chemoPv↑, 2, ChemoSideEff↓, 1, neuroP↑, 1, NP/CIPN↓, 1, QoL↑, 1, radioP↑, 1, RenoP↑, 2, toxicity↓, 3, TumVol↓, 4, TumW↓, 2, Weight∅, 1,
Infection & Microbiome(tgid=24) ⓘ
Bacteria↓, 1, CD8+↑, 2,
Total Targets: 404
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiArt↑, 1, AntiBio↑, 2, antiD↓, 1, compII↑, 1, Stroke↓, 2,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 11, Catalase↑, 4, GPx↑, 2, GSH↑, 5, GSTs↑, 1, HO-1↑, 2, Keap1↑, 1, lipid-P↓, 1, MDA↓, 3, MPO↓, 1, NRF2↑, 2, ROS↓, 10, ROS∅, 3, SOD↑, 4, SOD2↑, 1, TBARS↓, 1, uricA↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↑, 2, compIII↑, 1, MMP↑, 2,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ALAT↓, 2, BUN↓, 1, p‑CREB↑, 1, LDL↓, 1, NADPH↑, 1,
Cell Death(tgid=5) ⓘ
Akt↑, 1, Apoptosis↓, 1, BAX↓, 1, Bcl-2↑, 1, Casp12↓, 1, Casp3↓, 1, Cyt‑c↓, 1, GranB/GZMB↓, 1, iNOS↓, 3, p‑JNK↓, 1, p38↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
AntiThr↑, 2, other↑, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↓, 1, p‑eIF2α↓, 1, ER Stress↓, 1, GRP78/BiP↓, 1, XBP-1↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
LC3‑Ⅱ/LC3‑Ⅰ↑, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
ERK↑, 1, mTOR↓, 1, PI3K↑, 1,
Migration(tgid=13) ⓘ
5LO↓, 1, APP↓, 1, MMP13↓, 1, PAI-1/SERPINE1↓, 1, TGF-β↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
ATF4↓, 1, NO↑, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 1, GastroP↑, 1, IBI↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CD4+↑, 2, COX2/PTGS2↓, 4, IFN-γ↓, 1, IL10↑, 1, IL1β↓, 2, IL4↓, 1, IL6↓, 2, IL6↑, 1, Imm↑, 2, Inflam↓, 8, Inflam↑, 1, LPS↓, 1, NF-kB↓, 3, TNF-α↓, 3,
Synaptic & Neurotransmission(tgid=18) ⓘ
AChE↓, 1, BChE↓, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 2, BACE/β-secretase↓, 2, NLRP3↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 1, BioAv↑, 3, BioAv↝, 2, Dose↝, 2, eff↓, 1, eff↑, 3,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 2, AST↓, 3, creat↓, 2, GutMicro↑, 1, IL6↓, 2, IL6↑, 1, Urea↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 1, AntiDiabetic↑, 1, antiPs↑, 1, cardioP↑, 5, chemoPv↑, 2, cognitive↑, 2, hepatoP↑, 6, memory↑, 2, motorD↑, 1, neuroP?, 1, neuroP↑, 7, Obesity↓, 1, Pain↓, 2, RenoP↑, 3, toxicity↓, 5, Wound Healing↑, 1,
Infection & Microbiome(tgid=24) ⓘ
AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 3, CD8+↑, 1, Diar↓, 1, Sepsis↓, 2,
Total Targets: 116
Scientific Paper Hit Count for: XIAP, X-linked inhibitor of apoptosis protein (XIAP) baculoviral IAP repeat-containing protein 4 (BIRC4)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:% Target#:396 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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