JAK2 Cancer Research Results
JAK2, Janus kinase 2: Click to Expand ⟱
| Source: CGL-Driver Genes |
| Type: Oncogene |
A tyrosine kinase that plays a crucial role in the signaling pathways of various cytokines and growth factors. It is particularly important in hematopoiesis (the formation of blood cells) and immune responses.
JAK2 plays a significant role in cancer biology, particularly in hematological malignancies, where its expression and activity are often upregulated. Increased JAK2 activity is generally associated with worse prognosis in many cancers, indicating its potential role in promoting tumor growth and survival.
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Scientific Papers found: Click to Expand⟱
cl‑Casp8↑, apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP in BT-474 cells
cl‑Casp3↑,
p‑JAK1↓, apigenin reduced the expression of p-STAT3 as well as p-JAK1 and p-JAK2 (upstream kinases
of STAT3)
p‑JAK2↓,
p‑STAT3↓,
P53↑,
VEGF↓, pigenin also reduced the level of VEGF
Hif1a↓, apigenin suppressed the expression of p-STAT3 and HIF-1α that was up-regulated by CoCl2 (hypoxia mimic)
MMP9↓,
TumCG↓, Apigenin suppresses the growth of BT-474 cells
TumCCA↑, The growth-suppressive activity of apigenin is accompanied by an increase in the sub-G 0 /G 1 apoptotic population in BT-474 cells
cl‑PARP↑,
cl‑Casp8↑, Apigenin induces apoptosis via caspase‑dependent pathways in SKBR3 cells.
cl‑Casp3↑,
VEGF↓,
TumCG↓, Apigenin suppresses the growth of SKBR3 cells.
TumCCA↑, Growth‑suppressive activity of apigenin is accompanied by an
increase in the sub G0/G1 apoptotic population in SKBR3 cells.
cl‑PARP↑, induced PARP cleavage in SKBR3 cells
p‑STAT3↓, apigenin reduced the expression of p-STAT3 and p-JAK2 in SKBR3 cells.
p‑JAK2↓,
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in-vitro, |
BC, |
MDA-MB-231 |
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cl‑Casp8↑, cleaved
cl‑Casp3↑, cleaved
cl‑PARP↑, cleaved
BAX∅, failed to regulate
Bcl-2∅, failed to regulate
Bcl-xL∅, failed to regulate
p‑STAT3↓,
P53↑,
P21↑,
p‑JAK2↓, p-JAK2
VEGF↓,
JAK2↓,
STAT3↓,
MMP2↓,
MMP9↓,
Mcl-1↓,
Bcl-xL↓,
cycD1/CCND1↓,
VEGF↓,
TumCCA↑, G1 cell cycle arrest in HNSCC
ChemoSen↑, DHA also synergized with cisplatin in tumor inhibition in HNSCC cells
RadioS↑, Our results demonstrated that BE significantly increased radiosensitivity in vitro and in vivo and enhanced apoptosis in tumor tissues
p‑STAT3↓, BE significantly downregulated the expression of p-STAT3, JAK2, and PD-L1, and significantly upregulated SOCS3 expression.
JAK2↓,
PD-L1↓,
SOCS-3↑,
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in-vitro, |
Nor, |
RAW264.7 |
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*p‑STAT1↓, Baicalein significantly reduced the phosphorylation of STAT1 and STAT3 and the phosphorylation of JAK1 and JAK2
*p‑STAT3↓,
*p‑JAK1↓,
*p‑JAK2↓,
*iNOS↓, inhibited production of iNOS upon LPS-stimulation
*NO↓, inhibition of releases of NO and pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, in a dose-dependent manner
*IL1β↓,
*IL6↓,
*TNF-α↓,
*ROS↓, baicalein reduced the LPS-induced accumulation of ROS
*AntiCan↓, Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation
*Inflam↓,
TumCP↓,
NF-kB↓, baicalein decreased the activation of nuclear factor-κB (NF-κB)
PPARγ↑, anti-inflammatory effects of baicalein might be initiated via PPARγ activation.
TumCCA↑, baicalein inhibited cell cycle progression and cell growth, and promoted apoptosis of cancer cells
JAK2↓, inactivation of the signaling pathway JAK2/STAT3 [63]
STAT3↓,
TumCMig↓, baicalein suppressed migration as well as invasion through decreasing the aerobic glycolysis and expression of MMP-2/9 proteins.
Glycolysis↓,
MMP2↓,
MMP9↓,
selectivity↑, Furthermore, baicalein and baicalin had less inhibitory effects on normal ovarian cells’ viability.
VEGF↓, baicalein is more effective in inhibiting the expressions of VEGF, HIF-1α, cMyc, and NFκB
Hif1a↓,
cMyc↓,
ChemoSen↑, baicalein enhanced the cisplatin sensitivity of SGC-7901/DDP gastric cancer cells by inducing autophagy and apoptosis through the Akt/mTOR and Keap 1/Nrf2 pathways
ROS↑, oral squamous cell carcinoma Cal27 cells. Significantly, it was noticed that baicalein activated reactive oxygen species (ROS) generation in Cal27 cells
p‑mTOR↓, results suggest that p-mTOR, p-Akt, p-IκB, and NF-κB protein expressions were decreased
PTEN↑, Baicalein upregulated PTEN expression, downregulated miR-424-3p, and downregulated PI3K and p-Akt.
*hepatoP↑, baicalein significantly ameliorated APAP-exposed liver damage and histological hepatocyte changes
*MDA↓, baicalein (50 or 100 mg/kg) pretreatment significantly inhibited liver MDA level (p < 0.05; Figure 4), increased SOD, CAT and GSH activity.
*SOD↑,
*Catalase↑,
*GSH↑,
*MAPK↓, Baicalein Prevented the MAPK Pathway Activation
*p‑JAK2↓, BAI Suppressed the Expression of p-JAK2 and p-STAT3 Proteins in APAP Liver Injury
*p‑STAT3↓,
*ALAT↓, our experimental results suggested that serum ALT and AST levels were obviously alleviated by Baicalein in a dose-dependent manner
*AST↓,
*ROS↓, hepatoprotective role of BAI via attenuating oxidative stress
*antiOx↑, hepatoprotective activity of Baicalein might be associated with its antioxidative capacity.
*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
*antiOx↑,
*cardioP↑,
*neuroP↑,
TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
cycD1/CCND1↓,
cycE/CCNE↓,
CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
mTOR↝,
Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
Casp9↑,
Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
TumCI↓,
EMT↓,
MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
E-cadherin↓,
Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
GRP78/BiP↓, Downregulates GRP78
EGFR↓, Downregulates EGFR
CDK4↓, downregulates CDK4, TERT, and TERC
COX2/PTGS2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
PGE2↓,
p‑JAK2↓,
p‑STAT3↓,
MMP2↓,
MMP9↓,
GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)
Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1/CCL2↓,
COX2/PTGS2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27/CDKN1B↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2/KDR/Flk1↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,
chemoPv↑, reviews about cancer chemopreventive role of betulinic acid against wide variety of cancers [18,19,20,21].
p‑STAT3↓, betulinic acid reduced the levels of p-STAT3 in tumor tissues derived from KB cells
JAK1↓, Betulinic acid exerted inhibitory effects on the constitutive phosphorylation of JAK1 and JAK2
JAK2↓,
VEGF↓, betulinic acid mediated inhibition of VEGF
EGFR↓, evaluation of betulinic acid as a next-generation EGFR inhibitor
Cyt‑c↑, release of SMAC/DIABLO and cytochrome c from mitochondria in SHEP neuroblastoma cells
Diablo↑,
AMPK↑, Betulinic acid induced activation of AMPK and consequently reduced the activation of mTOR.
mTOR↓,
Sp1/3/4↓, Betulinic acid significantly reduced the quantities of Sp1, Sp3 and Sp4 in the tissues of the tumors derived from RKO cells
DNAdam↑, Betulinic acid efficiently triggered DNA damage (γH2AX) and apoptosis (caspase-3 and p53 phosphorylation) in temozolomide-sensitive and temozolomide-resistant glioblastoma cells.
Gli1↓, Betulinic acid effectively reduced GLI1, GLI2 and PTCH1 in RMS-13 cells.
GLI2↓,
PTCH1↓,
MMP2↓, betulinic acid exerted inhibitory effects on MMP-2 and MMP-9 in HepG2 cells.
MMP9↓,
miR-21↓, Collectively, p53 increased miR-21 levels and inhibited SOD2 levels, leading to significant increase in the accumulation of ROS levels and apoptotic cell death.
SOD2↓,
ROS↑,
Apoptosis↑,
NRF2↓, Brusatol is a potent Nrf2 inhibitor for future cancer treatment.
TumCG↓, Brusatol exhibits significant tumor inhibition in multiple cancers.
ChemoSen↑, also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents
ROS↑, Graphical Abstract
NF-kB↓,
Akt↓,
mTOR↓,
TumCCA↑,
Apoptosis↑,
PARP↑,
Casp↑,
P53↓,
Bcl-2↓,
PI3K↓,
JAK2↓,
EMT↓,
p27/CDKN1B↑,
ROCK1↓,
MMP2↓,
MMP9↓,
NRF2↓, which is the reason why brusatol is called an Nrf2 inhibitor [15]. Brusatol is a potent Nrf2 inhibitor
AntiTum↑, Brusatol shows significant antitumor effects in vitro and in vivo
HO-1↓, Moreover, brusatol inhibited the expression of Nrf2 downstream genes, such as HO-1 [19], [31], [32], NQO1 [43], [44], VEGF [45], and AKR1C1 [46].
NQO1↓,
VEGF↓,
MRP1/ABCC1↓, brusatol reduced both the mRNA and protein levels of NQO1, HO-1, MDR1, and MRP5
RadioS↑, Improvement of sensitivity to radiotherapy and phototherapy
PhotoS↑,
toxicity↝, the toxicity of brusatol is a problem that can not be ignored.
*Inflam↓, anti-inflammatory, antimicrobial, antioxidant, and pro-proliferative effects.
*antiOx↑,
*ROS↓, The antioxidant properties of boron help protect cells from oxidative stress, a common feature of chronic wounds that can impair healing
*angioG↑, Boron compounds exhibit diverse therapeutic actions in wound healing, including antimicrobial effects, inflammation modulation, oxidative stress reduction, angiogenesis induction, and anti-fibrotic properties.
*COL1↑, Boron has been shown to increase the expression of proteins involved in wound contraction and matrix remodeling, such as collagen, alpha-smooth muscle actin, and transforming growth factor-beta1.
*α-SMA↑,
*TGF-β↑,
*BMD↑, Animals treated with boron showed favorable changes in bone density, wound healing, embryonic development, and liver metabolism
*hepatoP↑,
*TNF-α↑, BA elevates TNF-α and heat-shock proteins 70 that are related to wound healing.
*HSP70/HSPA5↑,
*SOD↑, antioxidant properties of BA showed that boron protects renal tissue from I/R injury via increasing SOD, CAT, and GSH and decreasing MDA and total oxidant status (TOS)
*Catalase↑,
*GSH↑,
*MDA↓,
*TOS↓,
*IL6↓, Boron supports gastric tissue by alleviating ROS, MDA, IL-6, TNF-α, and JAK2/STAT3 action, as well as improving AMPK activity
*JAK2↓,
*STAT3↓,
*AMPK↑,
*lipid-P↓, boron may improve wound healing by hindering lipid peroxidation and increasing the level of VEGF
*VEGF↑,
*Half-Life↝, Boron is a trace element, usually found at a concentration of 0–0.2 mg/dL in plasma with a half-life of 5–10 h, and 1–2 mg of it is needed in the daily diet
*ROS↓,
*MDA↓,
*TNF-α↓,
*IL6↓,
*JAK2↓,
*STAT3↓,
*AMPK↑,
*Sema3A/PlexinA1↑,
Hif1a↓, CVR showed an HIF-1α inhibitory potential, which is highly expressed in HCC tissues.
AFP↑, CVR/SOR enhanced liver functions and decreased AFP level.
hepatoP↑, CVR improves liver functions and enhances SOR anti-cancer activity
STAT3↓, CVR/SOR hindered HCC progression by downregulating STAT3, JAK2, and FGL1.
JAK2↓,
*CD8+↑, CVR/SOR induced tumor immunity via increasing CD8+ T cells.
ChemoSen↑, CVR/SOR is a powerful combination for tumor repression and enhancing SOR efficiency in HCC by modulating FGL1
Dose↝, 10 mg/kg SOR by intragastic tube for 6 weeks daily;
angioG↓, CVR improves SOR attenuation efficacy against TAA-induced angiogenesis
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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
toxicity⇅, Due to unfavorable toxicity profile and undefined mechanism, Celastrol's application in clinical cancer therapy remains limited.
toxicity↓, Celastrol has no obvious toxic effect at 1.5 mg/kg/day in a 15 days' administration
TumCG↓, Celastrol inhibits tumor growth and increases ROS in a STAT3 dependent manner in gastric and ovarian cancer celllines.
ROS↑,
IL6↓, downregulates IL-6 level and inhibits the JAK2/STAT3 signaling pathway by suppressing STAT3' activation
JAK2↓,
STAT3↓,
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NA, |
neuroblastoma, |
SH-SY5Y |
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AntiCan↑, Chaetocin is a fungal mycotoxin that extensively found in various natural products and has anticancer and anti‑inflammatory activities.
Inflam↓,
tumCV↓, chaetocin on cellular viability, apoptosis, cell migration, and invasion were investigated.
Apoptosis↑,
TumCMig↓, chaetocin significantly decreased the SHSY-5Y cell invasion and migration at 50 μM treatment
TumCI↓,
JAK2↓, increasing chaetocin treatments greatly decreased the activity of proteins connected to the JAK2/STAT3 signaling pathway
STAT3↓,
tumCV↓, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner.
TumCP↓,
Ki-67↓,
Apoptosis↓,
Inflam↓, inflammation- and oxidative- related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS, restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression
ROS↑,
MMP↓,
JAK2↓,
STAT3↓,
ERK↓,
MIP2↓, we found that crocin manifested an obvious inhibition of the contents of MIP-2, IL-6, MCP-1, IL-8, IL-1β, and TNF-α in HCT-116 cells in relative to the control group and the inhibitory effect of 200 μM
IL6↓,
MCP1/CCL2↓,
IL8↓,
IL1β↓,
TNF-α↓,
SOD↓, oxidative stress-related factors and confirmed that the contents of SOD, CAT, and GSH in HCT-116 cells were reduced by crocin in relative to the control group and the 200 μM
Catalase↓,
GSH↓,
ROS↑, crocin exhibited a notable increase production of ROS in HCT-116 cells
mtDam↑, crocin is inducing oxidative stress and damaging the mitochondria, leading to cell death.
STAT3↓, STAT3 inhibitory activity of the polymeric micellar cucurbitacins
toxicity↝, Interestingly, the toxicity associated with cucurbitacins I and B (figure 1. G, B) was significantly reduced when these drugs were loaded into the nanoparticles. (21)
COX2/PTGS2↓, Also, cucurbitacins are able to inhibit the activity of cyclooxygenases 2 (COX2)
TumCG↓, Growth inhibition was accompanied by cell cycle arrest and apoptosis in breast cancer cell lines (MCF-7 and MDA-MB-231) treated with cucurbitacins B and E
TumCCA↑,
Apoptosis↑,
STAT3↓, Cucurbitacins are recognized as anti-tumour agents involving - among other mechanisms - interference with STAT3 signaling,
JAK2↓, cucurbitacins’ inhibition of phosphorylation of STAT3 and/or JAK2 and their subsequent activation seamed as the major mechanism of their action
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vitro+vivo, |
Lung, |
A549 |
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in-vitro, |
BC, |
MDA-MB-453 |
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STAT3↓, five cucurbitacin (Cuc) analogs, A, B, E, I, and Q, led to the discovery of Cuc Q, which inhibits the activation of STAT3 but not JAK2;
JAK2↓, Cuc A which inhibits JAK2 but not STAT3 activation; and Cuc B, E, and I, which inhibit the activation of both.
TumCG↓, Cuc Q, but not Cuc A, suppresses tumor growth indicating that JAK2 inhibition is not sufficient to inhibit tumor growth
TumCCA↑, Cuc IIa induced the irreversible clustering of filamentous actin and arrested cell cycle by the increases in G2/M populations.
p‑H3↓, Cuc IIa resulted in the reduced phospho-Histone H3 and markedly increased cleavage of poly-(ADP-ribose) polymerase or PARP, immediate upstream of DNA breakdown as the result of caspase activation, consistent with mitotic blockage-induced cell death.
cl‑PARP↑,
Casp↑,
AntiCan↑, Cuc IIa is a novel class of anti-cancer drug in suppression of cancer cell expansion by disrupting the actin cytoskeleton and directing the cell to undergo PARP-mediated apoptosis through the inhibition of survivin downstream of JAK2/STAT3.
JAK2↓,
STAT3↓,
TumCG↓, cucurbitacin B was tested in vitro and in vivo against human pancreatic cancer cells. Dose-response studies showed that the drug inhibited 50% growth of seven pancreatic cancer cell lines at 10(-7) mol/L,
TumCCA↑, Cucurbitacin B caused dose- and time-dependent G(2)-M-phase arrest and apoptosis of pancreatic cancer cells.
Apoptosis↑,
JAK2↓, associated with inhibition of activated JAK2, STAT3, and STAT5, increased level of p21(WAF1) even in cells with nonfunctional p53, and decrease of expression of cyclin A, cyclin B1, and Bcl-XL with subsequent activation of the caspase cascade.
STAT3↓,
STAT5↓,
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
Bcl-xL↓,
ChemoSen↑, combination of cucurbitacin B and gemcitabine synergistically potentiated the antiproliferative effects of gemcitabine on pancreatic cancer cells.
TumVol↓, cucurbitacin B decreased the volume of pancreatic tumor xenografts in athymic nude mice by 69.2%
toxicity↓, without noticeable drug toxicities.
eff↑, Combined therapy with cucurbitacin B and gemcitabine at relatively low doses (0.5 mg·kg−1 and 25 mg·kg−1 respectively) resulted in highly significant tumour growth inhibition of pancreatic cancer xenografts (up to 79%)
TumCG↓,
Bcl-xL↓, mice who received both cucurbitacin B and gemcitabine, revealed stronger inhibition of Bcl-XL, Bcl-2 and c-myc, and higher activation of the caspase cascades, than mice treated with either agent alone.
Bcl-2↓,
cMyc↓,
Casp↑,
STAT3↓, Activated STAT3 and JAK2 were clearly inhibited in tumours of mice treated either with high-dose cucurbitacin B or the combination regimes
JAK2↓,
CSCs↓, In the present study, we tested the effects of curcumin on lung cancer stem-like cells and report that in addition to inhibition on the proliferation and colony formation of lung cancer cells, curcumin reduces tumor spheres of H460 cells
JAK2↓, via inhibiting the JAK2/STAT3 signaling pathway
STAT3↓,
TumCP↓, Curcumin inhibits proliferation and colony formation of
NCI-H460 lung cancer cells.
TumCG↓, Curcumin inhibits tumor spheres growth of NCI-H460 lung
cancer cells in vivo.
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Review, |
Var, |
NA |
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Review, |
AD, |
NA |
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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↑,
| - |
in-vitro, |
Thyroid, |
BCPAP |
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- |
in-vitro, |
Thyroid, |
TPC-1 |
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TumCI↓,
TumCI↓,
MMP2↓,
MMP9↓,
EMT↓,
STAT3↓,
miR-301a-3p↓,
STAT↓,
N-cadherin↓,
Vim↓,
Fibronectin↓,
p‑JAK↓,
p‑JAK2↓,
p‑JAK3↓,
p‑STAT1↓,
p‑STAT2↓,
E-cadherin↑,
HIF-1↓, Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF).
VEGF↓, Curcumin suppresses the HIF-1 pathway under hypoxia, which decreases VEGF expression in both tumour and stromal cells and suppresses angiogenesis.
angioG↓, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia.
RadioS↑, continued interest in curcumin is the molecules’ modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours.
ChemoSen↑, Combining cisplatin with curcumin promotes cell apoptosis through the YWHAG pathway and its interaction with HIF-1α, affecting the pentose phosphorylation pathway [
other↝, Cancer patients with hypoxia in their tumours have a poorer prognosis and are at greater risk of metastasis
Apoptosis↑, Curcumin exerts its unique anti-tumour efficacy primarily via pleiotropic functions resulting in apoptosis and decreased tumour cell growth and metastasis
TumCG↓,
TumMeta↓,
BioAv↓, However, due to its low water solubility and low chemical stability, curcumin’s use is limited.
COX2/PTGS2↓, abrogate the proliferation of pancreatic cancer cells through inhibition of COX-2, CD-31, VEGF, and IL-8 and suppression of TGF-β via NF-κB and HIF-1α downregulation
CD31/PECAM-1↓,
IL8↓,
TGF-β↓,
NF-kB↓,
JAK2↓, Curcumin application reduced tumourspheres of H460 cells via inhibition of the JAK2/STAT3 signalling pathway
STAT3↓,
| - |
vitro+vivo, |
HCC, |
HepG2 |
|
|
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- |
in-vitro, |
HCC, |
Hep3B |
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- |
in-vitro, |
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
ROS↑, FA showed promising anticancer activity through underlying mechanisms, including induction of oxidative stress, cytotoxic effect, cell cycle arrest, apoptotic effect, suppression of invasion and migration, antiproliferative effect, autophagy, and gen
TumCCA↑,
TumCI↓,
TumCMig↓,
TumCP↓,
BioAv↑, FA, indicating lower oral bioavailability is affected by the liver's fast conjugation process; this limitation is overcome by applying a nanoformulation of FA.
BioAv↑, medication's bioavailability is 100% when administered intravenously (IV)
TP53↑, FA could impede cell growth by upregulating the gene expression of TP53 and downregulating the gene expression of CDK2, CDK4, and CDK6 in prostate cancer PC-3 cells, resulting in cell cycle arrest in PC-3 cells
CDK2↓,
CDK4↓,
CDK6↓,
JAK2↓, blocking the JAK2/STAT6 immune signaling pathway
STAT6↓,
tyrosinase↓, FA could also decrease tyrosinase activity by directly binding to enzymes
p‑Akt↓, FA lowered phosphorylation of AKT and PI3K in CaSki cells in a dose-dependent way,
p‑PI3K↓,
mTOR↓, FA reduced the amount of mTOR mRNA and Ki-67 protein in A549 lung
Ki-67↓,
Casp3↑, increased the levels of caspase-3 protein
proCasp8↑, FA elevated pro-caspase-3, pro-caspase-8, and pro-caspase-9 and PARP cleavage, Bax, and ROS and decreased Bcl-2, Mcl-1, AKT, and PI3K pathway levels in a dose-dependent way
cl‑PARP↑,
BAX↑,
Bcl-2↓,
Mcl-1↓,
MMP9↓, reducing cell invasion, MMP9 mRNA expression, and cyclin D1 and cyclin E levels
cycD1/CCND1↓,
cycE/CCNE↓,
PINK1↑, FA (100 μg/mL) enhanced apoptosis via increasing PINK-1, Parkin and reducing the MMP expression
PARK2↑,
MMP↓,
CycD3↓, reducing the gene expressions of CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 level in PC-3 cells
TumAuto⇅, FA has shown anticancer activity via the increase and decrease of autophagy in different types of cancer.
eff↑, by combining with other compounds like 2-deoxy-D-glucose (2DG) [164], epirubicin, gamma radiation [165], aspirin, thyoquinine [166], phenolic and flavonoids, P-coumaric acid [167], 4-vinylguaiacol, caffeic [168], coumaric, and gemcitabine [169].
eff↑, FA and aspirin could trigger apoptotic cell death, p-RB, p21, and p-ERK1/2, cytotoxicity and reduce PCNA and MKI67, growth of tumor in pancreatic cancer.
ALAT↓, figure 5
AST↓,
ALP↓,
VEGF↓,
MMPs↓,
angioG↓,
AntiCan↑, FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity,
Inflam↓,
RadioS↑,
ROS↑, FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS)
Apoptosis↑,
TumCCA↑, G0/G1 phase
TumCMig↑, inducing autophagy; inhibiting cell migration, invasion, and angiogenesis
TumCI↓,
angioG↓,
ChemoSen↑, synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions.
ChemoSideEff↓,
P53↑, FA could increase the expression level of p53 in MIA PaCa-2 pancreatic cancer cells
cycD1/CCND1↓, while reducing the expression levels of cyclin D1 and cyclin-dependent kinase (CDK) 4/6.
CDK4↓,
CDK6↓,
TumW↓, FA treatment was found to reduce tumor weight in a dose-dependent manner, increase miR-34a expression, downregulate Bcl-2 protein expression, and upregulate caspase-3 protein expression
miR-34a↑,
Bcl-2↓,
Casp3↑,
BAX↑,
β-catenin/ZEB1↓, isoferulic acid dose-dependently downregulated the expression of β-catenin and MYC proto-oncogene (c-Myc), inducing apoptosis
cMyc↓,
Bax:Bcl2↑, FXS-3 can inhibit the activity of A549 cells by upregulating the Bax/Bcl-2 ratio
SOD↓, After treatment with FA, Cao et al. [40] observed an increase in ROS production and a decrease in superoxide dismutase activity and glutathione content in EC-1 and TE-4 oesophageal cancer cells
GSH↓,
LDH↓, FA could promote the release of lactate dehydrogenase (LDH)
ERK↑, A can activate the ERK1/2 pathway
eff↑, conjugated zinc oxide nanoparticles with FA (ZnONPs-FA) to act on hepatoma Huh-7 and HepG2 cells. The results showed that ZnONPs-FA could induce oxidative DNA damage and apoptosis by inducing ROS production.
JAK2↓, by inhibiting the JAK2/STAT6 immune signaling pathway
STAT6↓,
NF-kB↓, thus inhibiting the activation of NF-κB
PYCR1↓, FA can target PYCR1 and inhibit its enzyme activity in a concentration-dependent manner.
PI3K↓, FA inhibits the activation of the PI3K/AKT pathway
Akt↓,
mTOR↓, FA could significantly reduce the expression level of mTOR mRNA and Ki-67 protein in A549 lung cancer graft tissue
Ki-67↓,
VEGF↓,
FGFR1↓, FA is a novel FGFR1 inhibitor
EMT↓, FA can inhibit EMT
CAIX↓, selectively inhibit CAIX
LC3II↑, Autophagy vacuoles and increased LC3-II and p62 autophagy proteins were observed after treatment with this compound
p62↑,
PKM2↓, FA could inhibit the expression of PKM2 and block aerobic glycolysis
Glycolysis↓,
*BioAv↓, FA has poor solubility in water and a poor ability to pass through biological barriers [118]; therefore, the extent to which it is metabolized in vivo after oral administration is largely unknown
*JAK2↓, In the present study, formononetin was identified to act as a JAK2 inhibitor, similarly to tyrphostin AG 490 (AG490), by significantly inhibiting the phosphorylation and the mRNA expression levels of JAK2 and STAT in HUVECs exposed to high glucose le
*Casp3↑, formononetin and AG490 improved the viability of HUVECs and inhibited the protein expression levels of caspase‑3
*Inflam↓, formononetin and AG490 attenuated the inflammatory response in HUVECs by downregulating the protein and mRNA expression levels of interleukin (IL)‑1β and intercellular adhesion molecule 1 (ICAM‑1).
*IL1β↓,
*ICAM-1↓,
*AntiDiabetic↑, suggesting that formononetin may represent a novel potential therapeutic compound to treat diabetic vascular complications
tumCV↓, FT could significantly inhibit cell viability, and induce apoptosis.
Apoptosis↑,
STAT3↓, suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation
STAT5↓,
JAK1↓, correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells
JAK2↓,
cSrc↓,
ROS↑, and this effect was found to be mediated via an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance.
Casp3↑, induction of caspase-3 activation and cleavage of PARP
cl‑PARP↑,
*RenoP↑, Fucoidan exhibits significant anti-inflammatory effects in kidney protection.
*Inflam↓,
*antiOx↑, Antioxidant properties effectively reduce oxidative stress in renal tissues.
*ROS↓,
*BloodF↑, Enhances renal function by improving blood flow and diuresis.
*diuretic↑,
*BioAv↓, High-MW fucoidans often display stronger anticoagulant and viscosity-modulating effects. However, they may have limited oral bioavailability,
*BioAv↑, whereas low- to medium-MW fractions show improved tissue penetration, more favorable absorption, and can retain potent anti-inflammatory and anti-fibrotic activities, making them attractive for chronic kidney disease applications
*MAPK↓, (LMWF) has been reported in models of renal ischemia-reperfusion injury, where it inhibits the MAPK signaling pathway and subsequently reduces inflammation and fibrosis
*ERK↑, fucoidan can activate the ERK/MAPK signaling pathway, which plays a crucial role in preserving the endothelial glycocalyx in CKD
*NLRP3↓, fucoidan attenuates NLRP3 inflammasome activation and subsequent podocyte pyroptosis, ultimately leading to improved renal function and reduced inflammation in diabetic kidney disease (DKD)
*NRF2↑, By inhibiting ROS-generating systems (e.g., NADPH oxidase) and activating Nrf2-dependent transcription of antioxidant genes, fucoidan limits mitochondrial dysfunction and prevents oxidative injury to podocytes and tubular epithelial cells
*MDA↓, fucoidan nanoparticles significantly reduced levels of malondialdehyde (MDA), a marker of lipid peroxidation and oxidative stress, while simultaneously upregulating the levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx)
*SOD↑,
*GPx↑,
*Catalase↑, Altogether, fucoidan directly reduces renal oxidative stress by scavenging reactive oxygen species and upregulating endogenous antioxidant defenses (e.g., SOD, CAT, GPx) in tubular and glomerular cells, by suppressing upstream ROS generation
*lipid-P↓, fucoidan limits lipid peroxidation and DNA damage, thereby preserving podocyte integrity and tubular epithelial viability
*DNAdam↓,
*Fibrosis↓, Inhibition of fibrosis
*JAK2↓, fucoidan combats renal fibrosis is via the restriction of the JAK2/STAT3 signaling pathway.
*STAT3↓,
*uricA↓, By reducing serum uric acid levels, fucoidan significantly inhibits the activation of JAK2/STAT3, consequently decreasing the expression of key fibrotic markers such as collagen I and α-smooth muscle actin (α-SMA)
*COL1↓,
*α-SMA↓,
*SIRT1↑, fucoidan’s anti-fibrotic effects are further attributed to its activation of protective pathways such as Sirt-1, GLP-1R, and Nrf2/HO-1(
*HO-1↑,
*GLP-1R↑,
*HMGB1↓, Stimulating these protective pathways results in the inhibition of pro-fibrotic signaling cascades, including the HMGB1/RAGE/NF-κB/TGF-β1 pathway
*RAGE↓,
*NF-kB↓,
*TGF-β1↓,
*PI3K↓, Fucoidan also exhibits potential in curtailing the inflammatory processes associated with renal fibrosis through its inhibitory effects on the PI3K/Akt/NF-κB signaling cascade.
*Akt↓,
*GutMicro↑, research has elucidated the important role of gut microbiota in mediating the protective effects of fucoidan, suggesting that modulation of microbial communities may underlie its benefits in renal health
*SCFAs↑, Fucoidan’s positive impact on gut microbiota includes enhancing the production of short-chain fatty acids (SCFAs), especially butyrate, which are known to support gut integrity and overall health (
*Buty↑,
*IBI↑, Fucoidan's ability to enhance SCFA production has been linked to improved intestinal barrier integrity, a crucial factor in preventing the translocation of harmful substances into the bloodstream, which can exacerbate kidney injury
*TJ↑, Studies indicate that fucoidan can upregulate the expression of tight junction proteins, crucial for maintaining the integrity of the intestinal epithelium
*Dose↝, national approval in China for renal indications, indicate that fucoidan is generally safe at oral doses of 50–300 mg/day and up to 1–3 g/day in short‑ to mid‑term studies, with no major hematologic, hepatic, or renal toxicity reported.
AntiCan↑, Natural gallic acid (GA) is noted to have anticancer properties for oncogene expression, cycle arrest, apoptosis, angiogenesis, migration and metastasis in various cancers.
TumCCA↑,
angioG↓,
TumCMig↓,
TumMeta↓,
CSCs↓, In two types of embryonic CSCs, GA effectively induced cell death via late apoptosis
Apoptosis↑,
P21↑, GA showed the G0/G1 cell cycle arrest activity in embryonic CSCs by inducing the increase of p21, p27 and p53 expression and the decrease of CDK4, cyclin E and cyclin D1 expression.
P53↑,
p27/CDKN1B↑,
CDK4↓,
cycE/CCNE↓,
cycD1/CCND1↓,
SOX2↓, GA inhibited the expression levels of mRNA and protein for stem cell markers, such as SOX2, NANOG and OCT4, in NTERA-2 and NCCIT cells.
Nanog↓,
OCT4↓,
ROS↑, The induction of cellular and mitochondrial reactive oxygen species by GA also activated the cellular DNA damage response pathway by raising the phosphorylated-BRCA1, ATM, Chk1, Chk2 and histone.
DNAdam↑,
BRCA1↑,
ATM↑,
CHK1↑,
Chk2↑,
Histones↑,
TumCI↓, GA inhibited CSCs invasion and migration by inhibiting the expression of matrix metalloproteinase by the downregulation of EGFR/JAK2/STAT5 signaling pathway.
MMPs↓,
EGFR↓,
JAK2↓,
STAT5↓,
ROS↑, generation of reactive oxygen species is involved in STAT3 inhibitory effect of garcinol.
STAT3↓,
cSrc↓,
JAK1↓,
JAK2↓,
NF-kB↓,
TGF-β↓,
TumCG↓,
| - |
in-vitro, |
Thyroid, |
TPC-1 |
|
|
|
*Inflam↓, Geraniol possesses pharmacological properties, including anti-inflammatory, anti-cancer, and neuroprotective properties
AntiCan↑,
*neuroP↑,
tumCV↓, IC50 value of 25 μM, which decreases cell viability and inhibited cell proliferation.
TumCP↓,
ROS↑, It also increased the accumulation of intracellular ROS, which induces apoptosis in the TPC-1 cells due to the dissipation of membrane potential and disruption of mitochondria.
Apoptosis?,
MMP↓,
Bcl-2↓, substantial reduction in the mRNA level expressions of Bcl-2, Cyclin D1, c-Myc, COX-2, TNF-α, NF-κB, IL-6, and surviving.
cycD1/CCND1↓,
cMyc↓,
COX2/PTGS2↓,
TNF-α↓,
NF-kB↓,
IL6↓,
survivin↓,
BAX↑, It also upregulated the Bax and caspase-3 mRNA expression suggesting cell death-mediated apoptosis.
Casp3↑,
JAK2↓, geraniol effectively inhibited the JAK-2, STAT-3, and ERK signaling pathways depicting geraniol as a potential therapeutic molecule for thyroid cancer treatment
STAT3↓,
ERK↓,
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vitro+vivo, |
BC, |
MDA-MB-231 |
|
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- |
in-vitro, |
Pca, |
DU145 |
|
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- |
in-vitro, |
Liver, |
HepG2 |
|
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- |
in-vitro, |
Lung, |
A549 |
|
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|
TumCP↓, 6-shogaol (6SG), one of active ingredients in ginger (Zingiber officinale), is known to exhibit anti-proliferative, anti-metastatic, and pro-apoptotic activities through a mechanism that is not fully elucidated
TumMeta↓,
p‑STAT3↓, We found that 6SG strongly inhibited constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK2 and c-Src kinases and nuclear translocation of STAT3 on both MDA-MB231 and DU145 cells.
JAK2↓,
cSrc↓,
JNK↑, 6SG caused the activation of JNK, p38 MAPK, and ERK
p38↑,
ERK↑,
eff↓, Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented 6SG-induced apoptosis.
ROS↑, 6SG Induces ROS Generation in Breast Cancer Cells
cl‑PARP↑, SG induced apoptosis as characterized by cleavage of PARP, accumulation of cells in subG1 phase, positive Annexin V binding, down-regulation of STAT3-regulated proteins, and activation of caspase-8, -9, -3 in both MDA-MB231 cells
TumCCA↑,
Casp8↑,
Casp9↑,
Casp3↑,
eff↑, Compared with other analogues of 6SG, such as 6-gingerol (6G), 8-gingerol (8G), and 10-gingerol (10G), 6SG was found to be the most potent blocker of STAT3 activation.
Bcl-2↑, 6SG also suppressed the expression of STAT3-regulated gene products such as Bcl-2, Bcl-xL, and Survivin in tumor tissues.
Bcl-xL↓,
survivin↓,
MMP9↓, (MMP-9) and cyclooxygenase-2 (COX-2), is also regulated by STAT3 activation. We found that 6SG down-regulated the expression of metastatic proteins in a time-dependent manner (
COX2/PTGS2↓,
IAP1↓, consequently, this alkanone down-regulated the expression of STAT3-regulated gene products, including bcl-xl, bcl-2, IAP-1, survivin, cyclin D1, MMP-9 and COX-2; a
Dose?, 10mg/kg - 50mg/kg mouse
TumCG↓, Ginkgetin suppressed the growth of 786-O in dose and time-dependent manners with IC50 values of 7.23 μM.
Casp3↑, Ginkgetin induced apoptosis of 786-O cells and increased the levels of caspase-8, caspase-9, and caspase-3.
Casp8↑,
Casp9↑,
JAK2↓, Ginkgetin treated 786-O cells showed decreased levels of JAK2 and phosphorylated-STAT3
STAT3↓,
*Inflam↓, anti-inflammatory, antioxidant, antifibrotic, anticancer, neuroprotective, cardioprotective, metabolic regulatory and antibacterial activities.
*antiOx↓, GK markedly attenuates oxidative stress in diverse experimental models.
AntiCan↑,
*neuroP↑,
*cardioP↑,
*Bacteria↓,
*ROS↓, GK significantly reduces intracellular ROS levels and lipid peroxidation products in various cell lines under metabolic or inflammatory stress
*lipid-P↓,
*NRF2↓, Both in vitro and in vivo studies consistently show that GK upregulates Nrf2 expression and nuclear translocation while downregulating Keap1,
*Keap1↓,
*NF-kB↓, numerous in vitro and in vivo studies have demonstrated that GK suppresses the NF-κB pathway
*MAPK↓, animal models show that GK attenuates MAPK pathway activation
MMP2↓, In vitro and in vivo evidence indicates that GK downregulates matrix metalloproteinases, including MMP-2 and MMP-9
M2 MC↓,
JAK2↓, In multiple cancer models, GK suppresses the JAK2/STAT3 signaling axis, leading to reduced expression of proliferation- and survival-related genes
STAT3↓,
TumCP↓,
Casp↑, GK induces mitochondrial-dependent apoptosis characterized by caspase activation and modulation of Bcl-2 family proteins
ChemoSen↑, GK can synergize with conventional chemotherapeutic agents.
*BMD↑, figure 4
*Aβ↓, In Alzheimer’s disease, GK directly targets Aβ pathology by inhibiting β-secretase and modulating fibril formation, while in vivo it reduces Aβ burden and neuroinflammation, partly via NF-κB pathway suppression
*Stroke↓, In ischemic stroke and cerebral ischemia–reperfusion injury, GK consistently improves neurological outcomes by modulating interconnected pathways.
*BioAv↓, GK exhibits relatively low oral bioavailability due to its biflavonoid structure and high lipophilicity, which result in poor aqueous solubility and limited intestinal absorption
NF-kB↓, Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR)
STAT3↓,
EGFR↓,
mTOR↓,
BioAv↝, honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials
Inflam↓, inflammation, proliferation, angiogenesis, invasion and metastasis.
TumCP↓,
angioG↓,
TumCI↓,
TumMeta↓,
cSrc↓, STAT3 inhibition by honokiol has also been correlated with the repression of upstream protein tyrosine kinases c-Src, JAK1 and JAK2
JAK1↓,
JAK2↓,
ERK↓, by inhibiting ERK and Akt pathways (31) or by upregulation of PTEN
Akt↓,
PTEN↑,
ChemoSen↑, Chemopreventive/ chemotherapeutic effects of honokiol in various malignancies: preclinical studies
chemoP↑,
COX2/PTGS2↓, honokiol was found to inhibit UVB-induced expression of cyclooxygenase-2, prostaglandin E2, proliferating cell nuclear antigen and pro-inflammatory cytokines, such as TNF-α, interleukin (IL)-1β and IL-6 in the skin
PGE2↓,
TNF-α↓,
IL1β↓,
IL6↓,
Casp3↑, release of caspases-3, -8 and -9as well as poly (ADP-ribose) polymerase (PARP) cleavage and p53 activation upon honokiol treatment that led to DNA fragmentation
Casp8↑,
Casp9↑,
cl‑PARP↑,
DNAdam↑,
Cyt‑c↑, translocation of cytochrome c to cytosol in human melanoma cell lines
RadioS↑, liposomal honokiol for 24 h showed a higher radiation enhancement ratio (~ two-fold) as compared to the radiation alone,
RAS↓, Honokiol also caused suppression of Ras activation
BBB↑, honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth
BioAv↓, Due to the concerns about poor aqueous solubility, liposomal formulations of honokiol have been developed and tested for their pharmacokinetics
Half-Life↝, In another comparative study, plasma honokiol concentrations was maintained above 30 and 10 μg/mL for 24 and 48 hours, respectively, in liposomal honokiol-treated mice, whereas it fell quickly (less than 5 μg/mL) by 12 hours in free honokiol-treated
Half-Life↝, free honokiol has poor GIT absorption, bio-transformed in liver to mono-glucuronide honokiol and sulphated mono-hydroxyhonokiol, ~ 50% is secreted in bile, ~ 60-65% plasma protein bound with elimination half life of (t1/2) of 49.05 – 56.24 minutes.
toxicity↓, These studies suggest that honokiol either alone or as a part of magnolia bark extract does not induce toxicity in animal models and thus could be clinically safe
Dose↝, This study conducted in vivo and in vitro experiments to investigate the anti-lung cancer effect of ISL (50 mg/kg/d), in combination with Gem (50 mg/kg/3d) (ISL + Gem)
Apoptosis↑, ISL + Gem exerted its antitumor effects by promoting apoptosis and inhibiting the proliferation of lung cancer cells as well as their ability to invade and metastasize
TumCP↓,
TumCI↓,
TumMeta↓,
P21↑, In vitro studies confirmed that combined ISL and Gem treatment increased lncRNA-p21 expression in NSCLC cell lines
selectivity↑, lncRNA-p21 acts as a competing endogenous RNA (ceRNA) for miR-4534, which was significantly upregulated in NSCLC tissues compared to normal controls.
JAK2↓, ISL combined with Gem could effectively impede the progression of lung cancer partially through inactivating JAK2/STAT3 signaling pathway via lncRNA-p21/miRNA-4534 axis.
STAT3↓,
TumCG↓,
LC3II↑,
p62↓,
ATP↓,
Pyruv↓,
GlucoseCon↑, promoted glucose uptake
HK2↓,
PFK1↓,
GLUT4↓,
Glycolysis↓,
JAK2↓,
p‑STAT3↓,
p‑STAT5↓,
TumCP↓, anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes.
Apoptosis↓,
TumMeta↑,
angioG↓,
*antiOx↑, nimbolidehas been found to possess antioxidant effect and free radical scavenging activities.
*eff↑, In comparison to azadirachtin and ascorbic acid (vitamin C), nimbolide was shown to be a more potent antioxidant
Apoptosis↑, Nimbolide induces apoptosis through diverse molecular mechanism(s).
MOMP↑, Nimbolide disrupts MOMP, which promotes caspases activation leading to apoptosis.
CDK1↓, Nimbolide also reduces the level of CDKs and cyclins, causing cell cycle arrest.
TumCCA↑,
MAPK↓, Nimbolide also abrogates various signaling cascades including MAPK (ERK1/2), JAK2/STAT3 and PI3K/Akt, leading to suppression of proliferation of a wide variety of human cancer cells.
JAK2↓,
STAT3↓,
PI3K↓,
Akt↓,
TumCP↓,
*NRF2↑, Nimbolide disrupts the Nrf2-KEAP1 complex and promotes the release of Nrf2, thus increasing levels of antioxidant and detoxification enzymes.
NF-kB↓, Inhibition of the NF-κB pathway also reduces the dissociation of GSK-3β from β-catenin, hence restraining the Wnt/β-catenin
GSK‐3β↑,
Wnt↓,
β-catenin/ZEB1↓,
chemoPv↑, nimbolide showed remarkable chemopreventive property.
Bcl-xL↓, Nimbolide treatmentdecreased the expression of antiapoptotic proteins(Bcl-xL, Bcl-2, survivin, caspase inhibitor molecules) and increased the expression of proapoptotic proteins (cytochrome c, Bax, Bad, Bid, cleaved caspases) in prostate cancer cells
Bcl-2↓,
survivin↓,
Cyt‑c↑,
BAX↑,
BID↑,
cl‑Casp↑,
P53↑, nimbolide acted by up-regulation of p53 levelin HeLa cells, thereby priming these cells towards apoptosis by destabilizing the mitochondria
DR5↑, Nimbolide up-regulated the expression of both DR5 and DR4 in chronic myeloid leukemia (KBM-5), multiple myeloma (U266), embryonic kidney carcinoma (A293), pancreatic adenocarcinoma (AsPC-1), and breast adenocarcinoma (MDA-MB-231) cells
DR4↑,
ROS↑, nimbolide resulted in generation of reactive oxygen species (ROS)
lipid-P↑, ROS also induced lipid peroxidation of cellular membranes, generating toxic metabolites such as malondialdehyde (MDA) that can react with DNA to form adducts to induce apoptosis.
MDA↑,
MMP2↓, nimbolide reduced mRNA expression of MMP-2, MMP-9, uPA and uPA receptor in breast cancer cells (MCF-7)
MMP9↓,
uPA↓,
ICAM-1↓, nimbolide was shown to downregulate the expression of MMP-9, ICAM-1, and CXCR4 in colorectal cancer xenografts
CXCR4↓,
CXCR2↓, nimbolide also reduced expression of CXCL8 and CXCR2 in breast cancers, and thus abrogated angiogenesis
angioG↓,
BBB↑, nimbolide might be able to cross blood-brain barrier (BBB) and the concentration could be sufficient for nimbolide to suppress intracranial tumour cell proliferation.
| - |
in-vitro, |
Pca, |
DU145 |
|
|
|
- |
in-vitro, |
Pca, |
LNCaP |
|
|
|
TumCP↓, PEITC significantly inhibited DU145 cell proliferation in a dose-dependent manner and induced the cell arrest at G2-M phase.
TumCCA↑,
STAT3↓, PEITC inhibited both constitutive and interleukin 6 (IL-6)-induced STAT3 activity in DU145 cells.
p‑JAK2↓, IL-6-stimulated phosphorylation of JAK2, an STAT3 upstream kinase, was also attenuated by PEITC.
eff↓, antioxidant reagent, N-acetyl-l-cysteine (NAC) which suppresses reactive oxygen species (ROS) generation, reversed the early inhibitory effects of PEITC on cell proliferation
TumCCA↑, PEITC Inhibits cell growth and induces G2-M phase cell cycle arrest in PCa cells
AR↓, PEITC inhibits IL-6-induced AR transcriptional activity in LNCaP cells
ROS↑, consistently suggest that PEITC induced ROS at early time of its application which in turn interfered with STAT3 activation with consequent cell growth inhibition.
tumCV↓, inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases,
TumCP↓,
TumCI↓,
angioG↓,
EMT↓,
TumMeta↓,
*hepatoP↑, A study demonstrated the hepatoprotective effects of P. longum via decreasing the rate of lipid peroxidation and increasing glutathione (GSH) levels
*lipid-P↓,
*GSH↑,
cardioP↑, cardioprotective effect
CycB/CCNB1↓, downregulated the mRNA expression of the cell cycle regulatory genes such as cyclin B1, cyclin D1, cyclin-dependent kinases (CDK)-1, CDK4, CDK6, and proliferating cell nuclear antigen (PCNA)
cycD1/CCND1↓,
CDK2↓,
CDK1↓,
CDK4↓,
CDK6↓,
PCNA↓,
Akt↓, suppression of the Akt/mTOR pathway by PL was also associated with the partial inhibition of glycolysis
mTOR↓,
Glycolysis↓,
NF-kB↓, Suppression of the NF-κB signaling pathway and its related genes by PL was reported in different cancers
IKKα↓, inactivation of the inhibitor of NF-κB kinase subunit beta (IKKβ)
JAK1↓, PL efficiently inhibited cell proliferation, invasion, and migration by blocking the JAK1,2/STAT3 signaling pathway
JAK2↓,
STAT3↓,
ERK↓, PL also negatively regulates ERK1/2 signaling pathways, thereby suppressing the level of c-Fos in CRC cells
cFos↓,
Slug↓, PL was found to downregulate slug and upregulate E-cadherin and inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells
E-cadherin↑,
TOP2↓, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8
P53↑,
P21↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
p‑HER2/EBBR2↓, ↓p-HER1, ↓p-HER2, ↓p-HER3
HO-1↑, ↑Apoptosis, ↑HO-1, ↑Nrf2
NRF2↑,
BIM↑, ↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt
p‑FOXO3↓,
Sp1/3/4↓, ↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET
cMyc↓,
EGFR↓,
survivin↓,
cMET↓,
NQO1↑, G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,
SOD2↑,
TrxR↓, G2/M cell cycle arrest, ↑apoptosis,
↑ROS, ↓GSH, ↓TrxR
MDM2↓, ↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis
p‑eIF2α↑,
ATF4↑,
CHOP/DDIT3↑,
MDA↑, ↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA
Ki-67↓, ↓Ki-67, ↓MMP-9, ↓Twist,
MMP9↓,
Twist↓,
SOX2↓, ↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug
Nanog↓,
OCT4↓,
N-cadherin↓,
Vim↓,
Snail↓,
TumW↓, ↓Tumor weight, ↓tumor growth
TumCG↓,
HK2↓, ↓HK2
RB1↓, ↓Rb
IL6↓, ↓IL-6, ↓IL-8,
IL8↓,
SOD1↑, ↑SOD1
RadioS↑, ombination with PL, very low intensity of radiation is found to be effective in cancer cells
ChemoSen↑, PL as a chemosensitizer which sensitized the cancer cells towards the commercially available chemotherapeutics
toxicity↓, PL does not have any adverse effect on the normal functioning of the liver and kidney.
Sp1/3/4↓, In vitro SKBR3 ↓Sp1, ↓Sp3, ↓Sp4
GSH↓, In vitro MCF-7 ↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα,
SOD↑, In vitro PANC-1, MIA PaCa-2 ↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1
| - |
in-vitro, |
Melanoma, |
U266 |
|
|
|
STAT3↓, plumbagin inhibited both constitutive and IL-6-inducible STAT3 phosphorylation in multiple myeloma (MM) cells
cSrc↓, his correlated with the inhibition of c-Src, JAK1, and JAK2 activation
JAK1↓,
JAK2↓,
SHP1↑, plumbagin induced the expression of the protein tyrosine phosphatase, SHP-1;
cycD1/CCND1↓, downregulated the expression of STAT3-regulated cyclin D1, Bcl-xL, and VEGF, activated caspase-3, induced PARP cleavage, and increased the sub-G1 population of MM cells.
Bcl-xL↓,
VEGF↓,
Casp3↑,
cl‑PARP↑,
TumCCA↑,
ChemoSen↑, sensitization of STAT3 overexpressing cancers to chemotherapeutic agents.
| - |
in-vitro, |
GC, |
NA |
|
|
|
- |
in-vivo, |
NA, |
NA |
|
|
|
TumCCA↑, significantly induced cell cycle arrest at G0/G1 and S phases
TumCP↓,
TumCMig↓,
TumCI↓,
TumVol↓,
TumW↓,
Weight∅, leaving mouse weight, liver function, and kidney function unaffected
JAK2↓,
STAT3↓,
| - |
Review, |
Var, |
NA |
|
|
|
- |
Review, |
Park, |
NA |
|
|
|
- |
Review, |
AD, |
NA |
|
|
|
JAK↓, plant polyphenols, especially quercetin, exert their inhibitory effects on the JAK–STAT pathway through known and unknown mechanisms.
STAT↓,
Inflam↓, quercetin significantly reduced levels of inflammation moderators, including NO synthase, COX-2, and CRP, in a human hepatocyte-derived cell line
NO↓,
COX2/PTGS2↓,
CRP↓,
selectivity↑, , quercetin is not harmful to healthy cells, while it can impose cytotoxic effects on cancer cells through a variety of mechanisms,
*neuroP↑, Alzheimer’s disease because of its antioxidant and anti-inflammatory activity.
STAT3↓, demonstrated as a suppressor of the STAT3 activation signaling pathway
cycD1/CCND1↓, Rb phosphorylation, cyclin D1 expression, and MMP-2 secretion are inhibited by 48 h treatment with 25 µM quercetin in T98G and U87 GBM cell lines
MMP2↓,
STAT4↓, by inhibiting IL-12-induced tyrosine phosphorylation of STAT3, STAT4, JAK2, and TYK2, quercetin inhibits the proliferation of T cells and differentiation of Th1
JAK2↓,
TumCP↓,
Diff↓,
*eff↑, administration of quercetin with piperine alone and in combination significantly prevented neuroinflammation via reducing the levels of IL-6, TNF-α (two potent activators of the JAK–STAT pathway), and IL-1β in PD in experimental rats
*IL6↓,
*TNF-α↓,
*IL1β↓,
*Aβ↓, quercetin suppressing β-secretase (an enzyme engaged in Aβ formation) and aggregation of Aβ
Showing Research Papers: 1 to 50 of 63
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 63
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
NAT↓, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
Catalase↓, 1, GSH↓, 3, HO-1↓, 1, HO-1↑, 3, lipid-P↑, 1, MDA↑, 2, NQO1↓, 1, NQO1↑, 2, NRF2↓, 2, NRF2↑, 1, PARK2↑, 1, PYCR1↓, 1, ROS↑, 18, SOD↓, 2, SOD↑, 1, SOD1↑, 1, SOD2↓, 1, SOD2↑, 1, TrxR↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 2, CDC2↓, 1, FGFR1↓, 1, MEK↓, 1, MMP↓, 4, mtDam↑, 1, PINK1↑, 1, Raf↓, 1, XIAP↓, 4,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ALAT↓, 1, AMPK↑, 2, AMPK↝, 1, CAIX↓, 1, cMyc↓, 5, GlucoseCon↑, 1, Glycolysis↓, 5, Histones↑, 1, HK2↓, 2, LDH↓, 1, PFK1↓, 1, PKM2↓, 1, PPARγ↑, 1, Pyruv↓, 1, p‑S6K↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 7, Akt↑, 2, p‑Akt↓, 1, Apoptosis?, 1, Apoptosis↓, 2, Apoptosis↑, 14, BAX↑, 5, BAX∅, 1, Bax:Bcl2↑, 2, Bcl-2↓, 11, Bcl-2↑, 1, Bcl-2∅, 1, Bcl-xL↓, 7, Bcl-xL∅, 1, BID↑, 1, BIM↑, 1, Casp↑, 4, cl‑Casp↑, 1, Casp3↑, 13, cl‑Casp3↑, 3, Casp7↑, 1, Casp8↑, 5, cl‑Casp8↑, 3, proCasp8↑, 1, Casp9↑, 5, Chk2↑, 1, CK2↓, 1, Cyt‑c↑, 4, Diablo↑, 1, DR4↑, 1, DR5↑, 1, IAP1↓, 1, JNK↑, 1, MAPK↓, 1, Mcl-1↓, 5, MDM2↓, 1, MOMP↑, 1, p27/CDKN1B↑, 3, p38↑, 1, survivin↓, 7, Telomerase↓, 2,
Kinase & Signal Transduction(tgid=6) ⓘ
cSrc↓, 6, HER2/EBBR2↓, 1, p‑HER2/EBBR2↓, 1, SOX9?, 1, Sp1/3/4↓, 4,
Transcription & Epigenetics(tgid=7) ⓘ
EZH2↓, 1, p‑H3↓, 1, miR-21↓, 2, miR-27a-3p↓, 1, other↝, 1, PhotoS↑, 1, tumCV↓, 5,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↑, 1, p‑eIF2α↑, 1, GRP78/BiP↓, 1, HSP90↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
LC3II↓, 1, LC3II↑, 2, p62↓, 1, p62↑, 1, TumAuto⇅, 1,
DNA Damage & Repair(tgid=10) ⓘ
ATM↑, 1, BRCA1↑, 1, CHK1↑, 1, DNAdam↑, 5, DNMT1↓, 1, p16↑, 1, P53↓, 1, P53↑, 6, PARP↑, 1, cl‑PARP↑, 10, PCNA↓, 1, TP53↑, 2,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK1↓, 2, CDK2↓, 3, CDK4↓, 6, cycA1/CCNA1↓, 1, CycB/CCNB1↓, 2, cycD1/CCND1↓, 13, CycD3↓, 1, cycE/CCNE↓, 4, P21↑, 5, RB1↓, 1, TumCCA↑, 21,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
CD133↓, 1, cFos↓, 1, cMET↓, 1, CSCs↓, 4, Diff↓, 2, EMT↓, 7, ERK↓, 5, ERK↑, 2, p‑FOXO3↓, 1, Gli1↓, 1, GSK‐3β↑, 1, miR-34a↑, 1, mTOR↓, 6, mTOR↝, 1, p‑mTOR↓, 1, p‑mTORC1↓, 1, n-MYC↓, 1, Nanog↓, 3, Nestin↓, 1, NOTCH↓, 1, NOTCH1↓, 1, OCT4↓, 3, PI3K↓, 4, p‑PI3K↓, 1, PTCH1↓, 1, PTEN↑, 4, RAS↓, 1, SHP1↑, 2, SOX2↓, 4, Src↓, 1, STAT↓, 2, p‑STAT1↓, 1, p‑STAT2↓, 1, STAT3↓, 33, p‑STAT3↓, 8, STAT4↓, 1, STAT5↓, 3, p‑STAT5↓, 1, STAT6↓, 2, TOP2↓, 1, TumCG↓, 14, tyrosinase↓, 1, Wnt↓, 1,
Migration(tgid=13) ⓘ
CD31/PECAM-1↓, 1, CXCL12↓, 1, E-cadherin↓, 1, E-cadherin↑, 2, Fibronectin↓, 1, GLI2↓, 1, Ki-67↓, 4, LAMs↓, 1, miR-301a-3p↓, 1, MMP2↓, 11, MMP9↓, 13, MMPs↓, 3, N-cadherin↓, 2, ROCK1↓, 1, Slug↓, 1, Snail↓, 1, TGF-β↓, 3, TumCI↓, 12, TumCMig↓, 7, TumCMig↑, 1, TumCP↓, 17, TumMeta↓, 6, TumMeta↑, 1, Twist↓, 1, uPA↓, 2, Vim↓, 2, α-SMA↓, 1, β-catenin/ZEB1↓, 2,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 10, ATF4↑, 1, EGFR↓, 6, HIF-1↓, 2, Hif1a↓, 5, NO↓, 1, VEGF↓, 15, VEGFR2/KDR/Flk1↓, 1, ZBTB10↑, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 2, GLUT4↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CCR7↓, 1, COX2/PTGS2↓, 8, CRP↓, 1, CXCR2↓, 1, CXCR4↓, 2, ICAM-1↓, 1, IKKα↓, 1, IL1β↓, 2, IL6↓, 8, IL8↓, 3, Inflam↓, 7, JAK↓, 1, p‑JAK↓, 1, JAK1↓, 7, p‑JAK1↓, 1, JAK2↓, 38, p‑JAK2↓, 6, p‑JAK3↓, 1, M2 MC↓, 1, MCP1/CCL2↓, 2, MIP2↓, 1, NF-kB↓, 12, PD-L1↓, 1, PGE2↓, 4, SOCS-3↑, 1, TNF-α↓, 3,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
AR↓, 2, CDK6↓, 3,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 3, BioAv↑, 4, BioAv↝, 1, ChemoSen↑, 17, Dose?, 2, Dose↓, 1, Dose↑, 1, Dose↝, 2, eff↓, 2, eff↑, 9, eff↝, 2, Half-Life↝, 2, MRP1/ABCC1↓, 1, RadioS↑, 7, selectivity↑, 4,
Clinical Biomarkers(tgid=22) ⓘ
AFP↑, 1, ALAT↓, 1, ALP↓, 1, AR↓, 2, AST↓, 1, BRCA1↑, 1, CRP↓, 1, EGFR↓, 6, EZH2↓, 1, GutMicro↑, 1, HER2/EBBR2↓, 1, p‑HER2/EBBR2↓, 1, IL6↓, 8, Ki-67↓, 4, LDH↓, 1, PD-L1↓, 1, TP53↑, 2,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 6, AntiTum↑, 1, cardioP↑, 1, chemoP↑, 1, chemoPv↑, 2, ChemoSideEff↓, 1, hepatoP↑, 1, toxicity↓, 4, toxicity⇅, 1, toxicity↝, 2, TumVol↓, 2, TumW↓, 3, Weight∅, 1,
Total Targets: 284
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
Buty↑, 1, diuretic↑, 1, GLP-1R↑, 1, SCFAs↑, 1, Stroke↓, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 1, antiOx↑, 6, Catalase↑, 3, GPx↑, 1, GSH↑, 3, HO-1↑, 1, Keap1↓, 1, lipid-P↓, 4, MDA↓, 5, NRF2↓, 1, NRF2↑, 2, ROS↓, 8, SOD↑, 4, TOS↓, 1, uricA↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ALAT↓, 1, AMPK↑, 2, SIRT1↑, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 1, Casp3↑, 1, iNOS↓, 1, MAPK↓, 3,
Protein Folding & ER Stress(tgid=8) ⓘ
HSP70/HSPA5↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↓, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
ERK↑, 1, PI3K↓, 1, p‑STAT1↓, 1, STAT3↓, 3, p‑STAT3↓, 2,
Migration(tgid=13) ⓘ
COL1↓, 1, COL1↑, 1, Fibrosis↓, 1, RAGE↓, 1, Sema3A/PlexinA1↑, 1, TGF-β↑, 1, TGF-β1↓, 1, TJ↑, 1, α-SMA↓, 1, α-SMA↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↑, 1, NO↓, 1, NO↑, 1, VEGF↑, 1,
Barriers & Transport(tgid=15) ⓘ
IBI↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
HMGB1↓, 1, ICAM-1↓, 1, IL1β↓, 3, IL6↓, 4, Inflam↓, 8, p‑JAK1↓, 1, JAK2↓, 4, p‑JAK2↓, 2, NF-kB↓, 2, TNF-α↓, 3, TNF-α↑, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 2, NLRP3↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 4, BioAv↑, 1, Dose↝, 1, eff↑, 2, Half-Life↝, 1,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 1, AST↓, 1, BloodF↑, 1, BMD↑, 2, GutMicro↑, 1, IL6↓, 4, RAGE↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↓, 1, AntiDiabetic↑, 1, cardioP↑, 2, cognitive↑, 1, hepatoP↑, 4, memory↑, 1, neuroP↑, 5, RenoP↑, 1, toxicity↓, 1,
Infection & Microbiome(tgid=24) ⓘ
Bacteria↓, 1, CD8+↑, 1,
Total Targets: 85
Scientific Paper Hit Count for: JAK2, Janus kinase 2
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#:164 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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