AIF Cancer Research Results

AIF, Apoptosis-Inducing Factor: Click to Expand ⟱

Source:

Type:

AIF is a mitochondrial oxidoreductase that contributes to cell death programmes and participates in the assembly of the respiratory chain.
Nuclear translocation of AIF occurs during cell death and has been associated with human disorders. Expression Levels:
AIF is often found to be overexpressed in several types of cancers, including breast, lung, and colorectal cancers.
The expression of AIF can vary significantly between different tumor types and even among patients with the same type of cancer.
Survival Rates:
High levels of AIF expression have been associated with poor prognosis in certain cancers, indicating a potential role in tumor aggressiveness and metastasis.
Conversely, low AIF expression may correlate with better survival outcomes in some contexts.
Overexpression: In many cancers, AIF is overexpressed, which is often associated with poor prognosis, increased tumor aggressiveness, and resistance to therapy.

Scientific Papers found: Click to Expand⟱

5269-

3BP,

The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models.

in-vitro,

HCC,

toxicity↑, 3-Bromopyruvate (3BP), a small alkylating agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK- cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.

5468-

AF,

The gold complex auranofin: new perspectives for cancer therapy

Review,

Var,

TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

5356-

AL,

Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects

Review,

GC,

Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

234-

AL,

Allicin Induces Anti-human Liver Cancer Cells through the p53 Gene Modulating Apoptosis and Autophagy

in-vitro,

HCC,

Hep3B

 0, 15, 20, 25, 35, 40 and 50 Î¼M of allicin for 24 h

 35 uM @24h

ROS↑, increased the production of ROS levels at 1, 3, 6 h. I
*toxicity∅, In other study, allicin treatment did not increase the leakage of lactate-dehydrogenase (LDH) of primary rat hepatocytes until 1 mM allicin treated with rat hepatocytes24. For this reason, allicin could be inferred as safe to normal liver cells
MMP↓, Allicin decreased mitochondrial membrane potential
BAX↑,
Bcl-2↓,
AIF↑,
Casp3↑, protein expression levels of caspase-3, -8, -9 increased after allicin treatment
Casp8↑,
Casp9↑,
eff↓, Allicin significantly induced ROS overproduction, whereas NAC pretreatment decreased the ROS induction by allicin exposure in Hep 3B cells
γH2AX↑, significant increase in the expression of γ-H2AX was observed at the initial stages (3, 6 h), but not at the later stages of 12, 24, 48 h
selectivity↑, data suggested that allicin induced apoptosis in p53-deficiency human liver carcinoma cells but caused autophagy in p53-normal function human liver carcinoma cells.
DNA-PK↑, increases production of ROS, triggers DNA damage

1563-

Api,

MET,

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells

in-vitro,

Nor,

HDFa

metformin (5 mM), apigenin (1 or 20 µM),

in-vitro,

PC,

AsPC-1

in-vitro,

PC,

MIA PaCa-2

in-vitro,

Pca,

DU145

in-vitro,

Pca,

LNCaP

in-vivo,

NA,

mice

selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

566-

ART/DHA,

2DG,

Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells

in-vitro,

Lung,

A549

in-vitro,

Lung,

PC9

GlucoseCon↓,
ATP↓,
lactateProd↓,
p‑S6↓,
mTOR↓,
GLUT1↓,
Casp9↑,
Casp8↑,
Casp3↑,
Cyt‑c↑,
AIF↑,
ROS↑, generation of ROS is critical for the toxic effects of DHA

5591-

BetA,

Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment

Review,

BC,

IC50 values ranging from 1 to 13.0 μg mL−1

BioAv↓, However, its poor water solubility limits its optimal therapeutic potential.
BioAv↑, nano-drug delivery systems (NDDSs) have gained significant attention as a method to substantially improve low solubility and poor drug bioavailability, enhance targeted drug delivery, and reduce side effects.
selectivity↑, reviews by Simone Fulda23,24 strengthened BA's potential for cancer treatment and prevention, particularly its ability to selectively trigger apoptosis in cancer cells while causing minimal harm to normal cells.
eff↑, It is important to note that the anticancer effects of BA on different types of tumors are more potent at a pH lower than 6.8.34
angioG↓, figure 3
*antiOx↑,
*Inflam↓,
MMP↓, BA-induced mitochondrial depolarization
Bcl-2↓, BA treatment has been shown to lower Bcl-2 expression and increase Bax, resulting in the activation of caspase-9 and caspase-3 through the mitochondrial pathway.63
BAX↑,
Casp9↑,
Casp3↑,
GRP78/BiP?, BA directly targets GRP78, triggering ER stress by activating the PERK-eIF2α-CHOP apoptotic cascade
ER Stress↑,
PERK↑,
CHOP↑,
ChemoSen↑, BA's ability to chemosensitize BC cells to taxanes highlights its importance in situations of drug resistance
SESN2↑, Under hypoxia, BA strongly increases SESN2 expression.
ROS↑, Reducing SESN2 levels enhances BA-induced ROS production, DNA damage, and radiosensitivity, while decreasing autophagic flux, indicating that SESN2-mediated autophagy serves as a protective adaptive response.68
MOMP↓, decreases the mitochondrial outer membrane potential (MOMP),
MAPK↑, This leads to the activation of p38 Mitogen-activated protein kinase (p38 MAPK), the release of cytochrome C, apoptosis-inducing factor (AIF),
Cyt‑c↑,
AIF↑,
STAT3↓, BA suppresses the signal transducer and activator of transcription (STAT) 3 signaling pathways
FAK↓, BA's inhibition of STAT3, as well as FAK, leads to decreased expression of MMPs and elevated TIMP-2, thereby impairing cancer cell migration and invasion
TIMP2↑,
TumCMig↓,
TumCI↓,
Sp1/3/4↓, Sp inhibition reduces cancer gene expression, inhibiting cancer cell growth.
TumCCA↑, It increases cell numbers in the G2/M phase, leading to cell cycle arrest.
DNAdam↑, causes DNA damage, thereby inhibiting the progression and invasion of cancer cells.

5584-

BetA,

Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors

in-vitro,

GBM,

A172

in-vitro,

GBM,

U118MG

in-vitro,

GBM,

U251

Apoptosis↑, BetA induced apoptosis by a direct effect on mitochondria independent of accumulation of wild-type p53 protein and independent of death-inducing ligand/receptor systems such as CD95.
P53↑,
Cyt‑c↑, release of soluble apoptogenic factors such as cytochrome c or AIF from mitochondria into the cytosol, where they induced activation of caspases.
AIF↑,
Casp↑,
AntiTum↑, BetA exhibited potent antitumor activity on neuroblastoma cells resistant to CD95- or doxorubicin-triggered apoptosis and on primary tumor cells from patients with neuroectodermal tumors.
MMP↓, BetA resulted in loss of the mitochondrial membrane potential

2735-

BetA,

Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications

Review,

Var,

mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-ÎºB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-ÎºB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2748-

BetA,

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Review,

Var,

Bcl-2↓, Cell death stimuli activate prodeath BCL-2 family proteins that in turn permeabilize mitochondrial outer membrane, thereby resulting in the release of Cyt C
MMP↓,
Cyt‑c↑,
Casp↑, Smac (second mitochondria-derived activator of caspase)/DIABLO (direct inhibitor of apoptosis [IAP] binding protein with low pI), and AIF (apoptosis-inducing factor) into the cytoplasm (27
Diablo↑,
AIF↑,
angioG↓, BetA's inhibition of growth-factor-induced angiogenesis seems at least partially owing to modulation of mitochondrial function in endothelial cells
BioAv↓, Current methods of conventional drug delivery using oral liquids or tablets are generally inefficient, with poor biodis- tribution, low solubility, long-term toxicity, and limited drug efficacy due to partial biodegradation, swelling, and ero- sion
NF-kB↓, BetA treatment inhibits the activation of NF-kB

2776-

Bos,

Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities

Review,

Var,

*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)

1448-

Bos,

A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells

in-vitro,

AML,

HL-60

12ug/ml

TumCP↓,
Apoptosis↑,
ROS↑, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation
NO↑,
cl‑Bcl-2↑,
BAX↑, translocation of Bax to mitochondria
MMP↓, loss of mitochondrial membrane potential
Cyt‑c↑, release of cytochrome c to the cytosol
AIF↑, release to the cytosol
Diablo↑, release to the cytosol
survivin↓,
ICAD↓,
Casp↑,
cl‑PARP↑,
DR4↑,
TNFR 1↑,

5836-

CAP,

In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway

vitro+vivo,

PC,

AsPC-1

pancreatic tumor xenografts in athymic nude mice

in-vitro,

PC,

Bxpc-3

tumCV↓, Treatment of AsPC-1 and BxPC-3 cells with capsaicin resulted in a dose-dependent inhibition of cell-viability and induction of apoptosis
Apoptosis↑,
ROS↑, which was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential.
MMP↓,
eff↓, These effects were significantly blocked when the cells were pretreated with a general antioxidant N-acetyl cysteine (NAC).
BAX↑, Exposure of AsPC-1 and BxPC-3 cells to capsaicin was also associated with increased expression of Bax, down-regulation of bcl-2, survivin and significant release of cytochrome c and AIF in the cytosol.
Bcl-2↓,
survivin↓,
Cyt‑c↑,
AIF↑,
selectivity↑, above-mentioned effects were not observed in the normal acinar cells in response to capsaicin-treatment.
JNK↑, Capsaicin-treatment resulted in the activation of JNK and JNK inhibitor SP600125 afforded protection against capsaicin-induced apoptosis.
TumCG↓, Furthermore, capsaicin when given orally markedly suppressed the growth of AsPC-1 pancreatic tumor xenografts in athymic nude mice, without side effects.

161-

CUR,

MeSA,

Enhanced apoptotic effects by the combination of curcumin and methylseleninic acid: potential role of Mcl-1 and FAK

in-vitro,

BC,

MDA-MB-231

in-vitro,

Pca,

DU145

Mcl-1↑, CUR alone
Mcl-1↓, CUR+MeSA
MPT↑,
AIF↑, An Enhanced AIF Nuclear Translocation Was Detected in the Combination-Treated MDA-MB-231 Cells
chemoPv↑, Curcumin and methylseleninic acid (MSeA) are well-documented dietary chemopreventive agents.
Apoptosis↑, Combining MSeA With Curcumin Resulted in a Significantly Enhanced Apoptotic Effect in MDA-MB-231 and DU145 Cells
ROS↑, a significantly increased ROS generation was detected in curcumin-treated cells, whereas no change was observed in MSeA-treated cells at both 3 and 6 h posttreatment.
FAK↓, Curcumin-induced FAK inhibition
STAT3↓, Previous studies showed that curcumin was capable of inhibiting activity of STAT3 and NF kB [37]. Indeed, we confirmed these effects in MDA-MB-231 cells
NF-kB↓,

167-

CUR,

Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria

in-vitro,

Pca,

PC3

MAPK↑,
JNK↑,
Casp3↑, Caspase-3, caspase-8, and caspase-9 were activated, and cytochrome c and apoptosis-inducing factor (AIF) were released from mitochondria following curcumin treatment
Casp8↑,
Casp9↑,
AIF↑, released from mitochondria
GSH↓, Curcumin treatment of PC3 cells caused time- and dose-dependent induction of apoptosis and depletion of cellular reduced glutathione (GSH).
eff↓, Exogenous GSH and its precursor N-acetyl-cysteine, but not ascorbic acid (AA) or ebselen, decreased curcumin accumulation in PC3 cells and also prevented curcumin-induced DNA fragmentation.
Apoptosis↑, Curcumin Triggers Apoptosis in Prostate Cancer Cells
DNAdam↑, curcumin-induced DNA fragmentation in PC3 cells was prevented in the presence of exogenous GSH or NAC.

1605-

EA,

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Review,

Var,

*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↓, 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

1329-

EMD,

Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells

in-vitro,

Tong,

SCC4

30 microM

TumCCA↑, S-phase arrest
eff↓, The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis
P53↑,
P21↑,
p27↑,
cycA1/CCNA1↓,
cycE/CCNE↓,
TS↓,
CDC25↓, Cdc25A
AIF↑, promoted the release of apoptosis-inducing factor (AIF)
proCasp9↓,
Cyt‑c↑,
MMP↓,
Bax:Bcl2↑,
Casp3↑,
Casp9↑,

2828-

FIS,

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

Review,

Var,

*neuroP↑, As a hydrophobic agent, FIS readily penetrates cell membranes and accumulates in cells to exert neuroprotective, neurotrophic and antioxidant effects
*antiOx↑,
*Inflam↓, FIS treatment may include alleviating inflammation, cell apoptosis and oxidative stress
RenoP↑, alleviates cell apoptosis and inflammation in acute kidney injury
COX2↓, FIS induces apoptosis in various tumor cells by, for example, inhibiting cyclooxygenase-2, inhibiting the Wnt/EGFR/NF-κB pathway, activating the caspase-3 cascade
Wnt↓,
EGFR↓,
NF-kB↓,
Casp3↑,
Ca+2↑, activating the caspase-3 and Ca2+ dependent endonuclease, and activating the caspase-8/caspase-3 dependent pathway via ERK1/2.
Casp8↑,
TumCCA↑, FIS controls the cell cycle and inhibits cyclin-dependent kinases (CDKs) in human cancer cell lines,
CDK1↓,
PI3K↓, by inhibition of PI3K/Akt/mTOR signaling [20], mitogen-activated protein kinases (MAPK) [21], and nuclear transcription factor (NF-κB)
Akt↓,
mTOR↓,
MAPK↓,
*P53↓, FIS inhibits aging by reducing p53, p21 and p16 expression in mouse and human tissues
*P21↓,
*p16↓,
mTORC1↓, FIS induces autophagic cell death by inhibiting both the mTORC1 and mTORC2 pathways
mTORC2↓,
P53↑, FIS significantly increases the expression of p53 and p21 proteins and lowers the levels of cyclin D1 [27,28], cyclin A, CDK4 and CDK2, thus contributing to cell-cycle arrest.
P21↑,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
BAX↑, FIS also increases Bax [27,28] and Bak [27] protein expression, but reduces the levels of Bcl-2 [27,28], Bcl-xL [27] and PCNA [28], and then starts the mitochondrial apoptotic pathway.
Bcl-2↓,
PCNA↓,
HER2/EBBR2↓, FIS reduces HER2 tyrosine phosphorylation in a dose-dependent manner and aids in proteasomal degradation of HER2 rather than lysosomal degradation
Cyt‑c↑, FIS cells causes destabilization of the mitochondrial membrane and an increase in cytochrome c levels, which is consistent with the loss of mitochondrial membrane integrity.
MMP↓,
cl‑Casp9↑,
MMP2↓, FIS reduces the enzymatic activity of both MMP-2 and MMP-9.
MMP9↓,
cl‑PARP↑, cell membrane, mitochondrial depolarization, activation of caspase-7, -8 and -9, and cleavage of PARP
uPA↓, interestingly, the promoter activity of the uPA gene is suppressed by FIS
DR4↑, induces upregulation of DR4 and DR5 death receptor expression in a dose-dependent manner
DR5↑,
ROS↓, FIS induces an increase in intracellular Ca2+ but reduces the production of ROS in WEHI-3 cells (myelomonocytic leukemia)
AIF↑, It also increases the levels of caspase-3 and AIF mRNA, but also increases necrosis markers including RIP3 and PARP1
CDC25↓, FIS reduces the expression of cdc25a, but increases the expression of p-p53, Chk1, p21 and p27, which may lead to a G0/G1 arrest.
Dose↑, FIS in concentrations from 0 to 10 μM does not affect cell viability; however, its use at concentrations of 20–40 μM significantly reduces the viability of lung cancer cells
CHOP↑, CaKi : FIS induces upregulation of CHOP expression and ROS production
ROS↑, NCI-H460 :FIS increases the ER stress signaling FIS increases the level of mitochondrial ROS FIS induces mitochondrial Ca2+ overloading and ER stress FIS induced ER stress-mediated cell death via activation of the MAPK pathway
cMyc↓, FIS influences proliferation related genes such as cyclin D1, c-myc and cyclooxygenase (COX)-2 by downregulating them.
cardioP↑, cardioprotective activity

2832-

FIS,

Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies

Review,

Var,

MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
Diablo↑,
Casp↑,
cl‑PARP↑,
Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
P21↑,
p27↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
Vim↓,
EMT↓,
Twist↓,
DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,

1967-

GamB,

Gambogic acid induces apoptotic cell death in T98G glioma cells

in-vitro,

GBM,

T98G

BAX↑, GA revealed apoptotic features including increased Bax and AIF expression, cytochrome c release, and cleavage of caspase-3, -8, -9, and PARP, while Bcl-2 expression was downregulated.
AIF↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↓,
Bcl-2↓,
ROS↑, GA induced reactive oxygen species (ROS) generation in T98G cells.

2919-

LT,

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence

Review,

Var,

RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
ChemoSen↑,
chemoP↑,
*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
*Catalase↑,
*SOD↑,
*GPx↑,
*GSTs↑,
*GSH↑,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*IL10↑,
NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
HO-1↓,
NQO1↓,
GSH↓,
MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
p‑MET↓,
p‑Akt↓,
HGF/c-Met↓,
NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
Bcl-2↓,
SOD2↓,
Casp8↑,
Casp3↑,
PARP↑,
MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
NLRP3↓,
ASC↓,
Casp1↓,
IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
IKKα↓,
p‑p65↓,
p‑p38↑,
MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
ICAM-1↓,
EGFR↑,
p‑PI3K↓,
E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
ZO-1↑,
N-cadherin↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
Vim↑,
ITGB1↓,
FAK↓,
p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
Rac1↓,
Cdc42↓,
Rho↓,
PCNA↓, Lung cancer model ↓Cyclin B1, ↑p21, ↑p-Cdc2, ↓Vimentin, ↓MMP9, ↑E-cadherin, ↓AIM2, ↓Pro-caspase-1, ↓Caspase-1 p10, ↓Pro-IL-1β, ↓IL-1β, ↓PCNA
Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
AXL↓,
CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
NSE↓,
SOD↓,
Catalase↓,
GPx↓,
GSR↓,
GSTs↓,
GSH↓,
VitE↓,
VitC↓,
CYP1A1↓,
cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
AR↓, ↓Androgen receptor
AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
VEGF↓,
H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
H4↓,
HDAC↓,
SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
Cyt‑c↑,
p‑JNK↑,
PTEN↓, Lung cancer model 1/5/10/30/50/80/100 μmol/L ↑Cleaved caspase-3, ↑PARP, ↑Bax, ↓Bcl-2, ↓EGFR, ↓PI3K/Akt/PTEN/mTOR, ↓CD34, ↓PCNA
mTOR↓,
CD34↓,
FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
Fas↑,
XIAP↓,
p‑eIF2α↑,
CHOP↑,
LC3II↑,
PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
STAT3↓,
IL2↑,
EMT↓, Luteolin exerts anticancer activity by inhibiting EMT, and the possible mechanisms include the inhibition of the EGFR-PI3K-AKT and integrin β1-FAK/Src signaling pathways
cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
*Half-Life↝, ats administered an intraperitoneal injection of luteolin (60 mg/kg) absorbed it rapidly as well, with peak levels reached at 0.083 h (71.99 ± 11.04 μg/mL) and a prolonged half-life (3.2 ± 0.7 h)
*eff↑, Luteolin chitosan-encapsulated nano-emulsions increase trans-nasal mucosal permeation nearly 6-fold, drug half-life 10-fold, and biodistribution of luteolin in brain tissue 4.4-fold after nasal administration

4947-

PEITC,

Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G0/G1 Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death

in-vitro,

Oral,

HSC3

AntiCan↑, Phenethyl isothiocyanate (PEITC), an effective anticancer and chemopreventive agent, has been reported to inhibit cancer cell growth through cell-cycle arrest and induction of apoptotic events in various human cancer cells models.
chemoPv↑,
TumCG↓,
Apoptosis↑,
TumCCA↑, PEITC effectively inhibited the HSC-3 cells’ growth and caused apoptosis. PEITC induced G0/G1 phase arrest through the effects of associated protein such as p53, p21, p17, CDK2 and cyclin E,
P53↑,
P21↑,
BAX↑, triggered apoptosis through promotion of Bax and Bid expression and reduction of Bcl-2, leading to decrease the levels of mitochondrial membrane potential (ΔΨm), and followed the releases of cytochrome c, AIF and Endo G then for causing apoptosis in
BID↑,
Bcl-2↓,
MMP↓,
Cyt‑c↑,
AIF↑,
ROS↑, PEITC promoted the production of ROS (Figure 4(a)) and Ca2+ (Figure 4(c)) but decreased the levels of ΔΨm
Ca+2↑,

4918-

PEITC,

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights

Review,

Var,

Apoptosis↑, Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and red
TumCP↓,
angioG↓,
TumMeta↓, reduction of metastasis (spread of cancer cells to new areas).
NF-kB↓, PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways.
Akt↓,
MAPK↓,
*BioAv↓, Isothiocyanates, including PEITC, are thermally labile, meaning they are susceptible to decomposition under heat;
ROS↑, Several studies proved that PEITC could initiate oxidative damage in the mitochondria by increasing the intracellular ROS to a highly toxic level
lipid-P↑, PEITC-induced ROS can cause lipid peroxidation of the mitochondrial membrane and, therefore, the loss of membrane integrity and the production of apoptosis-inducing factor (AIF) and apoptogenic cytochrome c (Cyt c)
AIF↑,
Cyt‑c↑,
DR4↑, PEITC can enhance TRAIL-induced apoptosis by upregulating DR4 and DR5 expression.
DR5↑,
TumCCA↑, Antiproliferative: Cell Cycle Arrest Induction
JAK↓, PEITC can hinder the activation of the JAK-STAT3 pathway,[112] decreasing the expression of MMP2 and MMP9.
STAT3↓,
MMP2↓,
MMP9↓,
PKCδ↓, efficacy of PEITC in inhibiting the protein kinase C (PKC)/MAPK pathway
Hif1a↓, PEITC can inhibit angiogenesis in cancer cells by suppressing the expression of HIF-1α
JNK↓, inhibiting the Akt pathway, activating Jun N-terminal kinase (JNK), and downregulating the Mcl-1
Mcl-1↓,
COX2↓, PEITC not only as a direct inhibitor of COX-2
MMP↓, 10 µm of PEITC caused ROS generation and mitochondrial depolarization, leading to the release of Cyt c and apoptosis mediated by activation of caspase-3, indicating that the mitochondrial membrane potential is compromised by ROS generation
Casp3↑,
ChemoSen↑, PEITC can synergize with cisplatin, doxorubicin, docetaxel, fludarabine, paclitaxel, gefitinib, or ionizing radiation to induce more pronounced apoptosis and growth inhibition in cancer than either agent alone
*BioAv↓, its low bioavailability impedes its clinical application as an oncologic treatment. PEITC is a lipophilic compound with poor water solubility, which hinders its dissolution and absorption in the gastrointestinal tract
Half-Life↓, Furthermore, rapid metabolism and elimination limit the systemic exposure of PEITC, reducing its efficacy against cancer cells.

4940-

PEITC,

Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G 0/G 1 Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death

in-vitro,

Oral,

HSC3

TumCCA↑, reported to inhibit cancer cell growth through cell-cycle arrest and induction of apoptotic events in various human cancer cells models
Apoptosis↑, PEITC induced cytotoxic effects on HSC-3 cells through the induction of apoptosis, and it also related to the involvement of ROS via mitochondria-dependent signal pathways.
BAX↑, it triggered apoptosis through promotion of Bax and Bid expression and reduction of Bcl-2, leading to decrease the levels of mitochondrial membrane potential (ΔΨm)
BID↑,
Bcl-2↓,
MMP↓,
Cyt‑c↑, and followed the releases of cytochrome c, AIF and Endo G then for causing apoptosis in HSC-3 cells.
AIF↑,
tumCV↓, PEITC Induced Cell-Morphological Changes and Decreased the Percentage of Viable Cells
ROS↑, We confirmed that whether PEITC-induced apoptosis is accompanied by the production of ROS and Ca2+ . PEITC promoted the production of ROS (Figure 4(a)) and Ca2+
Ca+2↑,
CDC25↓, PEITC decreased expression of cdc25A, CDK6 and cyclin D (Figure 5(a)), CDK2 and cyclin E (Figure 5(b)) proteins but increased the levels of p15
CDK6↓,
cycD1/CCND1↓,
CDK2↓,
cycE/CCNE↓,
P53↑, but increased the levels of p15 (Figure 5(a)), p53, p27, and p21 (Figure 5(b)) that led to G 0/G 1 phase arrest in HSC-3 cells.
p27↑,
P21↑,
Casp9↑, Here, we found that PEITC promoted ROS production and decreased the levels of ΔΨm and cytochrome c release, the activation of caspase-9 and caspase-3
Casp3↑,
GRP78/BiP↑, promotion of ROS and Ca2+ production that caused ER stress which based on increasing the GRP78 and ROS,

4942-

PEITC,

Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G(0)/G(1) Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death

in-vitro,

Oral,

HSC3

0.5, 1, 2, 2.5, and 5 μM) for 24, 48, or 72 h.

chemoPv↑, Phenethyl isothiocyanate (PEITC), an effective anticancer and chemopreventive agent, has been reported to inhibit cancer cell growth through cell-cycle arrest and induction of apoptotic events in various human cancer cells models
TumCG↓,
TumCCA↑,
Apoptosis↑, PEITC effectively inhibited the HSC-3 cells' growth and caused apoptosis.
BAX↑, triggered apoptosis through promotion of Bax and Bid expression and reduction of Bcl-2, leading to decrease the levels of mitochondrial membrane potential (ΔΨm),
BID↑,
Bcl-2↓,
MMP↓,
Cyt‑c↑, and followed the releases of cytochrome c, AIF and Endo G then for causing apoptosis in HSC-3 cells
AIF↑,
ROS↑, PEITC promoted the production of ROS (Figure 4(a)) and Ca2+
Ca+2↑,

5158-

PLB,

Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells

in-vitro,

Cerv,

ME-180

TumCG↓, plumbagin inhibits the growth of ME-180 cells in a concentration and time-dependent manner.
ROS↑, The cytotoxic effect of plumbagin induced cell death is through the generation of reactive oxygen species (ROS) and subsequent induction of apoptosis
Apoptosis↑,
MMP↓, plumbagin caused loss of mitochondrial membrane potential (DeltaPsi(m)),
DNAdam↑, DNA fragmentation
Cyt‑c↑, lumbagin-induced apoptosis involved release of mitochondrial cytochrome c and apoptosis inducing factor (AIF)
AIF↑,
Casp3↑, plumbagin-mediated activation of caspase-3 and -9
Casp9↑,
eff↓, Our results also show that pretreatment of ME-180 cells with NAC blocks plumbagin-induced loss of DeltaPsi(m) and subsequent release of cytochrome c, AIF, and caspase-9 and -3 activation,

91-

QC,

The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells

in-vitro,

Pca,

PC3

 50-200 uM

CDK2↓, decreasing the levels of CDK2, cyclins E, and D proteins
cycE/CCNE↓,
cycD1/CCND1↓, proteins
ATFs↑, Quercetin also stimulated the protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress
GRP78/BiP↑,
Bcl-2↓,
BAX↑, quercetin may induce apoptosis by direct activation of caspase cascade through mitochondrial pathway and ER stress in PC-3 cells.
Casp3↑, Quercetin Promoted the Activations of Caspase-3, -8, and -9 in PC-3 Cells
Casp8↑,
Casp9↑,
ER Stress↑, stress
CHOP↑,
TumCCA↑, quercetin at 150 μM caused G0/G1 phase arrest (31.4-49.7%) and sub-G1 phase cells (19.77%) for 36 h treatment and this effect is a time-dependent manner.
DNAdam↑, incubation with quercetin for 48 h showed an apoptotic cell death and DNA damage
AIF↑, quercetin promoted the trafficking of AIF protein released from mitochondria to nuclei.
Ca+2↑, quercetin-treated PC-3 cells led to the significant changes in Ca 21 concentrations of PC-3 cells from 3 h and up to 12 h [Fig. 4
MMP↓, quercetin significantly decreased the levels of DCm in PC-3 cells in a time-dependent course

3353-

QC,

Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells

in-vitro,

Oral,

KON

 0, 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, and 400 µg/mL

50ug/L @ 72h

in-vitro,

Nor,

MRC-5

tumCV↓, reduced the vitality of KON cells and had minimal effect on MRC cells.
selectivity↑, Owing to the appropriate dosages of quercetin needed to treat these diseases, normal cells do not exhibit any overtly harmful side effects.
TumCCA↑, quercetin increased the percentage of dead cells and cell cycle arrests in the S and G2/M phases.
TumCMig↓, quercetin inhibited KON cells’ capacity for migration and invasion in addition to their effects on cell stability and structure
TumCI↓,
Apoptosis↑, inducing apoptosis and preventing metastasis, quercetin was found to downregulate the expression of BCL-2/BCL-XL while increasing the expression of BAX.
TumMeta↓,
Bcl-2↓,
BAX↑,
TIMP1↑, TIMP-1 expression was upregulated while MMP-2 and MMP-9 were downregulated.
MMP2↓,
MMP9↓,
*Inflam↓, anti-inflammatory, anti-cancer, antibacterial, antifungal, anti-diabetic, antimalarial, neuroprotective, and cardioprotective properties.
*neuroP↑,
*cardioP↑,
p38↓, MCF-7 cells, quercetin successfully decreased the expression of phosphor p38MAPK, Twist, p21, and Cyclin D1
MAPK↓,
Twist↓,
P21↓,
cycD1/CCND1↓,
Casp3↑, directly aided by the significant increase in caspase-3 and − 9 levels and activities
Casp9↑,
p‑Akt↓, High quercetin concentrations also caused an inhibition of Akt and ERK phosphorylation
p‑ERK↓,
CD44↓, reduced cell division and triggered apoptosis, albeit to a lesser degree in CD44+/CD24− cells.
CD24↓,
ChemoSen↑, combination of quercetin and doxorubicin caused G2/M arrest in T47D cells, and to a lesser amount in cancer stem cells (CSCs) that were isolate
MMP↓, (lower levels of ΔΨ m), which is followed by the release of Cyto C, AIF, and Endo G from mitochondria, which causes apoptosis and ultimately leads to cell death.
Cyt‑c↑,
AIF↑,
ROS↑, Compared to the control group, quercetin administration significantly raised ROS levels at 25, 50, 100, 200, and 400 µg/mL.
Ca+2↑, increased production of reactive oxygen species and Ca2+, decreased levels of mitochondrial membrane potential (ΔΨ m),
Hif1a↓, Quercetin treatment resulted in a considerable downregulation of HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels in HOS cells.
VEGF↓,

3374-

QC,

Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis

Review,

Oral,

Review,

AD,

α-SMA↓, In oral cancer cells, quercetin could inhibit EMT via up-regulation of claudin-1 and E-cadherin and down-regulation of α-SMA, vimentin, fibronectin, and Slug [29]
α-SMA↑, OSC20 Invasion: ↓Migration, ↑Expression of epithelial markers (E-cadherin & claudin-1), ↑Expression of mesenchymal markers (fibronectin, vimentin, & α-SMA),
TumCP↓, quercetin significantly reduced cancer cell proliferation, cell viability, tumor volume, invasion, metastasis and migration
tumCV↓,
TumVol↓,
TumCI↓,
TumMeta↓,
TumCMig↓,
ROS↑, This anti-cancer agent induced oxidative stress and apoptosis in the cancer cells.
Apoptosis↑,
BioAv↓, The efficacy of quercetin (as lipophilic) is much impacted by its poor absorption rates, which define its bioavailability. The research on quercetin's bioavailability in animal models shows it may be as low as 10%
*neuroP↑, quercetin has been observed to exhibit neuroprotective effects in Alzheimer's disease through its anti-oxidants, and anti-inflammatory properties and inhibition of amyloid-β (Aβ) fibril formation
*antiOx↑,
*Inflam↓,
*Aβ↓,
*cardioP↑, Additionally, quercetin protects the heart by stopping oxidative stress, inflammation, apoptosis, and protein kinases
MMP↓, ↓MMP, ↑Cytosolic Cyt. C,
Cyt‑c↑,
MMP2↓, ↓Activation MMP-2 & MMP-9, ↓Expression levels of EMT inducers & MMPs, Downregulated Twist & Slug
MMP9↓,
EMT↓,
MMPs↓,
Twist↓,
Slug↓,
Ca+2↑, ↑Apoptosis, ↑ROS, ↑Ca2+ production, ↑Activities of caspase‑3, caspase‑8 & caspase‑9
AIF↑, ↑Mitochondrial release of Cyt. C, AIF, & Endo G
Endon↑,
P-gp↓, ↓ Protein levels of P-gp, & P-gp Expression
LDH↑, ↑LDH release
HK2↓, CAL27 cells) 80µM/24h Molecular markers: ↓Activities of HK, PK, & LDH, ↓Glycolysis, ↓Glucose uptake, ↓Lactate production, ↓Viability, ↓G3BP1, & YWHA2 protein levels
PKA↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
GRP78/BiP↑, Quercetin controls the activation of intracellular Ca2+ and calpain-1, which then activates GRP78, caspase-12, and C/EBP homologous protein (CHOP) in oral cancer cells
Casp12↑,
CHOP↑,

5125-

Sal,

Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma

in-vitro,

GBM,

ER Stress↑, SLM induces a potent endoplasmic reticulum (ER) stress followed by the trigger of the unfolded protein response (UPR) and an aberrant autophagic flux that culminated in necrosis due to mitochondria and lysosomal alterations.
UPR↑,
autoF↓, SLM treatment does not trigger apoptosis and blocks the autophagy flux in glioma cell line
lysosome↝,
ROS↑, aberrant autophagic flux was orchestrated by the production of Reactive Oxygen Species (ROS)
lipid-P↑, our data suggest that in our system the oxidative stress blocks the autophagic flux through lipid oxidation.
CSCs↓, SLM induces a potent antitumor effect in brain tumor stem cells (BTSCs) and established adult and pediatric glioma cell lines in vitro
necrosis↑, SLM induces necrosis cell death
ATP↓, with increasing doses of SLM displayed a decrease in intracellular ATP levels
MMP↓, SLM treated cells displayed significantly lower ΔΨm than untreated cells
MOMP↑, SLM induces mitochondrial MOMP.
DNAdam↑, We observed double strand breaks in SLM-treated cells (Figure 4C) and it is possible that this DNA damage is induced as a consequence of AIF internalization.
AIF↑,
lysoMP↑, hypothesis that SLM treatment triggers an autophagic process that cannot proceed adequately because of LMP resulting from oxidative stress.
MitoP↑, In addition, impairment of mitochondrial activity would trigger mitophagy, with engulfment of the organelle and initiation of autophagy.
Ca+2↑, The elevated levels of calcium and ROS inside mitochondria results in MOMP

1730-

SFN,

Sulforaphane: An emergent anti-cancer stem cell agent

Review,

Var,

BioAv↓, When exposed to high temperatures during meal preparation, myrosinase can be degraded, lose its function, and subsequently compromise the synthesis of SFN.
BioAv↑, eating raw cruciferous vegetables, instead of heating them can significantly improve the biodisponibility of SFN and its subsequent beneficial effects.
GSTA1↑, induction of Phase II enzymes [glutathione S-transferase (GST)
P450↓, (cytochrome P450, CYP) inhibition
TumCCA↑, herb-derived agent can also promote cell cycle arrest and apoptosis by regulating different signaling pathways including Nuclear Factor erythroid Related Factor 2 (Nrf2)-Keap1 and NF-κB.
HDAC↓, modulate the activity of some epigenetic factors, such as histone deacetylases (HDAC),
P21↑, upregulation of p21 and p27,
p27↑,
DNMT1↓, SFN was able to decrease the expression of DNMT1 and DNMT3 in LnCap prostate cancer cells
DNMT3A↓,
cycD1/CCND1↑, reduce methylation in Cyclin D2 promoter, thus inducing Cyclin D2 gene expression in those cells
DNAdam↑, SFN induced DNA damage, enhanced Bax expression and the release of cytochrome C followed by apoptosis
BAX↑,
Cyt‑c↑,
Apoptosis↑,
ROS↑, SFN increased reactive oxygen species (ROS), apoptosis-inducing factor (AIF)
AIF↑,
CDK1↑,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
NRF2↑, SFN significantly activated the major antioxidant marker Nrf2 and decreased NFκB, TNF-α, IL-1β
NF-kB↓,
TNF-α↓,
IL1β↓,
CSCs↓, SFN, have attracted attention due to their anti-CSC effect
CD133↓,
CD44↓,
ALDH↓,
Nanog↓,
OCT4↓,
hTERT/TERT↓,
MMP2↓,
EMT↓, SFN was reported to inhibit EMT and metastasis in the NSCLC, the cell lines H1299
ALDH1A1↓, ALDH1A1), Wnt3, and Notch4, other CSC-related genes inhibited by SFN treatment
Wnt↓,
NOTCH↓, SFN can inhibit aberrantly activated embryonic pathways in CSCs, including Sonic Hedgehog (SHH), Wnt/β-catenin, Cripto-1 (CR-1), and Notch.
ChemoSen↑, These results suggest that the antioxidant properties of SFN do not impact the cytotoxicity of antineoplastic drugs, but on the contrary, seems to improve it.
*Ki-67↓, Ki-67 and HDAC3 levels significantly decreased in benign breast tissues, and there was also a reduction in HDAC activity in blood cells
*HDAC3↓,
*HDAC↓,

1480-

SFN,

Sulforaphane Induces Cell Death Through G2/M Phase Arrest and Triggers Apoptosis in HCT 116 Human Colon Cancer Cells

in-vitro,

CRC,

HCT116

tumCV↓,
TumCCA↑, G2/M phase arrest
Apoptosis↑,
cycA1/CCNA1↑,
CycB/CCNB1↑,
CDC25↓, Cdc 25C
CDK1↓,
ROS↑, SFN induced the generation of reactive oxygen species (ROS)
eff↓, Ca[Formula: see text] and decreased mitochondria membrane potential and increased caspase-8, -9 and -3 activities in HCT 116 cell
Cyt‑c↑,
AIF↑,
ER Stress↑,

2227-

SK,

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

in-vitro,

GC,

BGC-823

13.35uM

in-vitro,

GC,

SGC-7901

9.63uM

in-vitro,

Nor,

GES-1

>20 μM

selectivity↑, In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells.
TumCP↓,
TumCD↑,
ROS↑, SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis.
MMP↓,
Casp↑, SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade
Cyt‑c↑,
Endon↑, nuclear translocation of AIF and Endonuclease G
AIF↑,
eff↓, NAC and GSH significantly inhibited SHK-induced death
ChemoSen↑, SHK enhances chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin
TumCCA↑, SHK caused S-phase cell cycle arrest in SGC-7901 and BGC-823 gastric cancer cells
GSH/GSSG↓, We found that the GSH/GSSG ratio was significantly decreased when treated with SHK.
lipid-P↑, SHK increases lipid peroxidation and induces apoptosis in vivo

5084-

SSE,

GEM,

The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

in-vitro,

PC,

PANC1

5.6uM

vitro+vivo,

PC,

Panc02

 4.6 µM,

C57BL mice bearing a Pan02-generated tumor

tumCV↓, Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ
ChemoSen↑,
TumCG↓, combined therapy not only inhibited tumor growth (65%)
OS↑, but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival.
MMP↓, sodium selenite induced mitochondrial depolarization
AIF↑, sodium selenite induced a large AIF nuclear location in both PANC-1 and Pan02 cells
GSH↓, selenite-mediated depletion of GSH and TRX
Trx↓,
ROS↑, selenite depletes GSH and reduced thioredoxin (TRX-H), leaving the cell defenseless against reactive oxygen species (ROS) and increasing them
AntiTum↑, sodium selenite should be considered as a promising antitumor agent against pancreatic cancer, either alone or in combination with GMZ.

2100-

TQ,

Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant

Review,

NA,

ROS⇅, Pubmed data indicated that NS has both anti-oxidant and pro-oxidant properties in different cell types
*antiOx↑, NS acts as an anti-oxidant by scavenging ROS [4]. It can ameliorate ischemic reperfusion injury conditions and attenuated ROS in heart [5] intestine [6] and kidney [7]
*SOD↑, improved the activities of various enzymes like superoxide dismutase [SOD] and myeloperoxidase (MPO)
*MPO↑,
*neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis, pilocarpine-induced seizures [25] and opioid tolerance
*chemoP↑, Anticancer drugs leave toxic effect due to over-production of ROS. NS oil or TQ can potentially up-regulate anti-oxidant mechanisms caused by anticancer drug
*radioP↑, NS seed extracts can protect normal tissue from oxidative damage during radiotherapy of cancer patients [35,36]
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells
IAP1↓, Anti-apoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc) and angiogenic genes (matrix metalloproteinase-9 orMMP-9) and vascular endothelial growth factor (VEGF) were down-regulated
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
ROS↑, TQ causes release of ROS in ABC cells which in turn inhibits NF-κB activity
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha (growth arrest and DNA damage inducible gene) and AIF
GADD45A↑,
AIF↑,
STAT3↓, TQ suppressed the STAT 3; the signal transducer and activator of transcription which is involved in the abnormal transformation of a number of human malignancies [53].

5904-

TV,

Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development

Review,

Var,

Review,

Stroke,

Review,

Diabetic,

Review,

Obesity,

Review,

AD,

Review,

Arthritis,

*antiOx↑, shown to possess various pharmacological properties including antioxidant, free radical scavenging, anti-inflammatory, analgesic, antispasmodic, antibacterial, antifungal, antiseptic and antitumor activities.
*ROS↓,
*Inflam↓,
*Bacteria↓,
AntiTum↑,
IronCh↑, chelation of metal ions
*HDL↑, antihyperlipidemic (via increasing the levels of high density lipoprotein cholesterol and decreasing the levels of low density lipoprotein cholesterol
*LDL↓,
*BioAv↝, videnced the presence of thymol in the stomach, intestine, and urine after its oral administration with sesame oil at a dose around 500 mg in rats and 1–3 g in rabbits.
*Half-Life↝, Oral administration of a single dose of thymol (50 mg/kg) was rapidly absorbed and slowly eliminated approximately within 24 h.The maximum concentration (Tmax) was reached after 30 min, while approximately 0.3 h was needed for the half-life
*BioAv↑, The rapid absorption of thymol indicates that it’s mainly absorbed in the upper component of the gut
*SOD↑, scavenging of free radicals by increasing the activities of several endogenous antioxidant enzymes levels viz. superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST)
*GPx↑,
*GSTs↑,
*eff↑, Thymol (0.02–0.20%) showed better antioxidant capacity than its isomer carvacrol in lipid systems due to its greater steric hindrance
radioP↑, Owing to its potent antioxidant potential, thymol showed radioprotective and anticlastogenic potential in gamma radiation induced Swiss albino mice
*MDA↓, Thymol supplementation increased the antioxidant status and decreased malondialdehyde (MDA) levels in broiler chickens
*other↑, Dietary supplementation with the combination of carvacrol–thymol (1:1) (100 mg/kg) reduced the occurrence of oxidative stress and the impairment of the intestinal barrier in weaning piglets by its potent antioxidant property
*COX1↓, by inhibiting both isoforms of cyclooxygenase (COX), with the most active being against COX-1 with an IC50 value of 0.2 μM.
*COX2↓,
*AntiAg↑, Thymol (1.1 μg/ml) exhibited inhibitory effects against arachidonic-acid-induced blood coagulation and platelet aggregation in vitro
*RNS↓, Thymol inhibited ROS (IC50= 3 μg/ml), reactive nitrogen species (RNS) (IC50= 4.7) and significantly reduced generation of NO and H2O2 as well as activities of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide reduced oxidase (NADH oxi
*NO↓,
*H2O2↓,
*NOS2↓,
*NADH↓,
*Imm↑, Thymol (25–200 mg/kg) was shown to modulate the immune system in cyclosporine-A treated Swiss albino mice by enhancing the expressions of cluster of differentiation 4 (CD4),
Apoptosis↑, anticancer actions of thymol include induction of apoptosis, anti-proliferation, inhibition of angiogenesis and migration
TumCP↓,
angioG↓,
TumCMig↓,
Ca+2↑, Intracellular Ca2+ overload
TumCCA↑, Cytotoxicity by stimulating cell cycle arrest in G0/G1 phase
DNAdam↑, DNA fragmentation, Bax protein expression, activation of caspase -9, -8 and -3 & concomitant PARP cleavage, AIF translocation
BAX↑,
Casp9↑,
Casp8↑,
Casp3↑,
cl‑PARP↑,
AIF↑,
i-ROS↑, intracellular ROS, depolarizing MMP, cytochrome-c release, cleavage of caspases, DNA fragmentation, activation of apaf-1,
MMP↓,
Cyt‑c↑,
APAF1↑,
Ca+2↑, In human glioblastoma cells, thymol (200–600 μM) produced a rise in (Ca2+)i levels
MMP9↓, diminished matrix metallopeptidase-9 (MMP9) and matrix metallopeptidase-2 (MMP2) production as well as protein kinase Cα (PKCα) and extracellular signal-regulated kinases (ERK1/2) phosphorylation
MMP2↓,
PKCδ↓,
ERK↓,
H2O2↑, Thymol increased the production of ROS and mitochondrial H2O2 thereby depolarizing mitochondrial membrane potential.
BAX↑, up-regulating Bcl-2 associated X protein (Bax) expression and down-regulating B-cell lymphoma (Bcl-2)
Bcl-2↓,
DNAdam↑, Thymol (IC50= 497 and 266 mM) was shown to induce DNA damage by increasing the levels of lipid peroxidation products;
lipid-P↑,
ChemoSen↑, This study recommended the combination of thymol with various chemotherapeutic agents to minimize its toxicity on normal cells and to improve the effectiveness of cancer treatment
chemoP↑,
*cardioP↑, significant increase in the activities of heart mitochondrial antioxidants (SOD, catalase, GPx, GSH)
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*BP↓, Thymol (1, 3, and 10 mg/kg) administration decreased the blood pressure and heart rate of Wistar rats whereas thymol (5 mg/kg) attenuated blood pressure in rabbits
*AntiDiabetic↑, protective effects of thymol in metabolic disorders such as diabetes mellitus and obesity
*Obesity↓,
RenoP↑, Thymol (20 mg/kg) was shown to inhibit cisplatin-induced renal injury by attenuating oxidative stress, inflammation and apoptosis in male adult Swiss Albino rats
*GastroP↑, This gastroprotective effect of thymol is believed to be due to increased mucus secretion
hepatoP↑, Thymol (150 mg/kg) showed to inhibit paracetamol induced hepatotoxicity in mice by preventing the alterations in the activities of hepatic marker enzymes
*AChE↓, Thymol (EC50= 0.74 mg/mL) was shown to possess acetylcholine esterase inhibitory activity but much less than its isomer carvacrol
*cognitive↑, Thymol (0.5–2 mg/kg) has been shown to inhibit cognitive impairments caused by increased Aβ levels or cholinergic hypofunction in Aβ
*BChE↓, whereas thymol (100 and 1000 μg/ml) also inhibited both AChE and butyrylcholinesterase (BChE) in a dose dependent manner
*other↓, Thymol (100 mg/kg) was shown to inhibit collagen induced arthritis by decreasing lipid peroxidation mediated oxidative stress by increasing the status of antioxidants in male Wistar rats
*BioAv↑, The encapsulation of thymol into methylcellulose microspheres by spray drying remarkably increases the bioavailability compared to free thymol

635-

VitC,

VitK3,

The combination of ascorbate and menadione causes cancer cell death by oxidative stress and replicative stress

in-vitro,

NA,

RNR↓, VC/VK3 inhibited RNR mainly by targeting its R2 subunit
GSH↓,
Trx1↓, increased highly oxidized Trx1 (oxidized (and generally less active) means effectively less)
GPx↓, VC/VK3 inhibited glutathione peroxidase activity and led to an elevated level of lipid peroxidation, which triggered apoptosis-inducing factor (AIF) mediated cell death pathway.
lipid-P↑,
AIF↑, which triggered apoptosis-inducing factor (AIF) mediated cell death pathway
ROS↑,

Showing Research Papers: 1 to 37 of 37

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 37

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 5, Catalase↑, 3, GPx↑, 3, GSH↑, 2, GSTs↑, 2, H2O2↓, 1, HDL↑, 1, lipid-P↓, 1, MDA↓, 1, MPO↑, 1, NADH↓, 1, NRF2↑, 1, RNS↓, 1, ROS↓, 1, SOD↑, 5,

Core Metabolism/Glycolysis ⓘ

LDL↓, 1,

Cell Death ⓘ

Casp3↓, 1, iNOS↓, 1, p‑JNK↓, 1, p38↓, 1,

Transcription & Epigenetics ⓘ

other↓, 1, other↑, 1,

DNA Damage & Repair ⓘ

p16↓, 1, P53↓, 1,

Cell Cycle & Senescence ⓘ

P21↓, 1,

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1, HDAC3↓, 1,

Migration ⓘ

5LO↓, 1, AntiAg↑, 1, Ki-67↓, 1, MMP3↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 2, NO↑, 1,

Barriers & Transport ⓘ

GastroP↑, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 2, COX2↓, 2, IL10↑, 1, IL1β↓, 2, IL6↓, 1, Imm↑, 1, Inflam↓, 5, PGE2↓, 1, PGE2↑, 1, Th1 response↓, 1, Th2↑, 2, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, BChE↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 3, BioAv↑, 2, BioAv↝, 1, eff↑, 2, Half-Life↝, 2,

Clinical Biomarkers ⓘ

BP↓, 1, GutMicro↑, 1, IL6↓, 1, Ki-67↓, 1, NOS2↓, 1,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, cardioP↑, 3, chemoP↑, 2, cognitive↑, 1, neuroP↑, 4, Obesity↓, 1, radioP↑, 1, toxicity∅, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 68

Scientific Paper Hit Count for: AIF, Apoptosis-Inducing Factor

4 Betulinic acid
4 Phenethyl isothiocyanate
3 Quercetin
2 Allicin (mainly Garlic)
2 Boswellia (frankincense)
2 Curcumin
2 Fisetin
2 Sulforaphane (mainly Broccoli)
1 3-bromopyruvate
1 Auranofin
1 Apigenin (mainly Parsley)
1 Metformin
1 Artemisinin
1 2-DeoxyGlucose
1 Capsaicin
1 methylseleninic acid
1 Ellagic acid
1 Emodin
1 Gambogic Acid
1 Luteolin
1 Plumbagin
1 salinomycin
1 Shikonin
1 Selenite (Sodium)
1 Gemcitabine (Gemzar)
1 Thymoquinone
1 Thymol-Thymus vulgaris
1 Vitamin C (Ascorbic Acid)
1 VitK3,menadione

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#:520  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

AIF Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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