CDK6 Cancer Research Results
CDK6, Cyclin-dependent kinase 6: Click to Expand ⟱
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Cyclin-dependent kinase 6 (CDK6) is another important regulator of the cell cycle, particularly involved in the transition from the G1 phase to the S phase.
CDK6 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker. Targeting CDK6 with specific inhibitors, such as palbociclib (which also targets CDK4), has shown promise in clinical settings, particularly in hormone receptor-positive breast cancer.
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Scientific Papers found: Click to Expand⟱
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
*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,
TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.
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in-vitro, |
Pca, |
DU145 |
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in-vitro, |
Pca, |
PC3 |
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TumCP↑, Here, we report that in vitro treatment of androgen-insensitive (DU145 and PC-3) and androgen-sensitive (LNCaP) prostate cancer cells with berberine inhibited cell proliferation and induced cell death in a dose-dependent (10–100 μmol/L) and time-depe
TumCCA↑, associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk.
p27↑,
Apoptosis↑, Berberine also significantly (P < 0.05–0.001) enhanced apoptosis of DU145 and LNCaP cells with induction of a higher ratio of Bax/Bcl-2 proteins
Bax:Bcl2↑,
MMP↓, disruption of mitochondrial membrane potential, and activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase.
Casp9↑,
Casp3↑,
PARP↑,
DNAdam↑, analysis of DNA fragmentation
selectivity↑, Berberine Inhibits Proliferation and Viability and Induces the Death of Prostate Cancer Cells but not of Normal Prostate Epithelial Cells
Cyt‑c↑, Berberine Induces the Disruption of Mitochondrial Membrane Potential and Increases the Release of Cytochrome c
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in-vitro, |
CRC, |
NA |
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in-vivo, |
NA, |
NA |
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5LO↓, boswellic acids, is known to be a non-redox and non-competitive inhibitor of 5-lipoxygenase
TumCG↓,
Let-7↑,
miR-200b↑, AKBA significantly up-regulated expression of the let-7 and miR-200 families in various CRC cell lines
NF-kB↓,
cMyc↓,
cycD1/CCND1↓,
MMP9↓,
CXCR4↓,
VEGF↓,
Bcl-xL↓,
survivin↓,
IAP1↓,
XIAP↓,
TumCG↓,
CDK6↓,
Vim↓,
E-cadherin↑,
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in-vivo, |
CRC, |
NA |
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in-vitro, |
CRC, |
HCT116 |
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in-vitro, |
CRC, |
RKO |
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in-vitro, |
CRC, |
SW480 |
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in-vitro, |
RCC, |
SW-620 |
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in-vitro, |
RCC, |
HT-29 |
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in-vitro, |
CRC, |
Caco-2 |
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miR-34a↑, curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells
miR-27a-3p↓,
TumCG↓,
BAX↑,
Bcl-2↓,
PARP1↓,
TumCCA↑,
Apoptosis↑,
cMyc↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
ChemoSen↑, combined treatment further increased the inhibitory effects
miR-34a↑, miR-34a expression was upregulated by curcumin and further elevated by concurrent treatment with curcumin and AKBA in HCT116 cell
miR-27a-3p↓,
chemoPv↑, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer.
TumCCA↑, The proposed anticancer mechanisms of capsaicin include an increase of cell-cycle arrest and apoptosis
Apoptosis↑,
ROS↑, Colo 205 150 Induced cell death, increased ROS and pro-apoptotic proteins
MMP↓, Human bladder cancer T24 100 Induced ROS production and mitochondrial membrane depolarization
Ca+2↑, capsaicin induces apoptosis in cancer cells is not completely elucidated but involves intracellular calcium increase, ROS, disruption of mitochondrial membrane transition potential, and activation of transcription factors such as NFκB and STATS (
JNK↑, studies performed in pancreatic cells showed that capsaicin apoptosis inducing effects were associated with ROS generation, JNK activation, mitochondrial depolarization, release of cytochrome c in the cytosol and activation of caspase-3 cascade
Casp3↑,
NADH↓, Capsaicin can also inhibit the plasma membrane NADH oxidase by functioning as a coenzyme Q antagonist.
CDK2↓, Capsaicin inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with the inhibition of CDK2, CDK4 and CDK6.
CDK4↓,
CDK6↓,
P53↑, capsaicin induces apoptosis in AGS cells through upregulation of p53 and that the apoptotic activity of capsaicin is p53-dependent.
*antiOx↑, antioxidant (8), anti-inflammatory (9) and anti-obesity (10) properties.
*Inflam↓,
*Obesity↓,
chemoPv↑, Many laboratories have reported that capsaicin possesses chemopreventive and chemotherapeutic effects
Apoptosis↑, Capsaicin has been shown to induce apoptosis in many different types of cancer cell lines including pancreatic (19) colonic (24), prostatic (25), liver (26), esophagieal (27), bladder (28), skin (29), leukemia (30), lung (31), and endothelial cells (
selectivity↑,
TRPV1↑, Transient receptor potential vanilloids (TRPVs) are receptors of capsaicin which lead to Ca2+-mediated mitochondrial damage and cytochrome c release.
Ca+2↑,
mtDam↑,
Cyt‑c↑,
P53↑, Capsaicin was found to induce p53 phosphorylation at the Ser-15 residue (30) and enhanced p53 acetylation through down-regulation of sirtuin 1 (
SIRT1↓,
TumCCA↑, Capsaicin induced G0/G1 phase arrest in human esophageal carcinoma cells with an increase of p21 and a decrease of CDK4, CDK6 and cyclin E (
P21↑,
CDK4↓,
CDK6↓,
cycE/CCNE↓,
angioG↓, Capsaicin has anti-angiogenic properties both in vitro and in vivo
TumMeta↓, Capsaicin treatment significantly reduced the metastatic burden in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (57).
tumCV↓, Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h
TumCCA↑, significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells
pRB↓, A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest
cycD1/CCND1↓,
CDK4↓,
CDK6↓,
PI3K↓, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions.
p‑Akt↓,
Apoptosis↑,
Bcl-2↓,
BAX↑,
TumCP↓, Celastrol affected the proliferation of U937 in a dose-dependent way, arresting the cell cycle at G0/G1 with 400 nM doses and triggering cell death with doses above 1000 nM.
TumCCA↑,
TumCD↑,
HSP90↓, Cell cycle arrest was accompanied by inhibition of HSP90 ATPase activity and elevation in HSP70 levels (a biochemical hallmark of HSP90 inhibition),
HSP70/HSPA5↑,
cycD1/CCND1↓, reduction in Cyclin D1, Cdk4 and Cdk6 levels
CDK4↓,
CDK6↓,
ATPase↓, celastrol's effects on ATPase activity in the protein complex pulled-down by anti-HSP90
*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
AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity
ROS↑, pomegranate ET inhibit pro-inflammatory pathways including, but not limited to, the NF-κB pathway, whose activation leads to immune reactions, inflammation, and the transcription of genes involved in cell survival, such as Bclx and inhibitors of apop
angioG↓, ET to inhibit angiogenesis
ChemoSen↑, ET could also be utilized to increase the sensitivity of tumor cells to standard chemotherapeutic drugs
BAX↑, induction of pro-apoptotic mediators (Bax and Bak), downregulation of Bcl-2 and Bcl-XL, and reduced expression of cyclin-dependent kinases 2, 4, 6, and cyclins D1, D2, and E
Bak↑,
Bcl-2↓,
Bcl-xL↓,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
cycE1↓,
TumCG↓, reduced LNCaP prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-α expression after four weeks of treatment in severe combined immunodeficient mice
VEGF↓,
Hif1a↓,
eff↑, Oenothein B, a macrocyclic ET, and quercetin-3-O-glucuronide from Epilobium sp. herbs—used in traditional medicine to treat benign prostatic hyperplasia and prostatic adenoma—have been proven to strongly inhibit the proliferation of human prostate ca
COX2↓, pomegranate ET (i.e., punicalagin and ellagic acid) have been shown to suppress cyclooxygenase-2 (COX-2) protein expression in human colon cancer (HT-29) cells
TumCCA↑, pomegranate ET and their metabolites, i.e., urolithins A and C, inhibit HT-29 cells proliferation via G0/G1 and G2/M arrest
selectivity↑, interestingly, normal human breast epithelial cells (MCF-10A) were far less sensitive to the inhibitory effect of polyphenol-rich fractions.
Wnt/(β-catenin)↓, suppression of Wnt/β-catenin
*toxicity∅, LD50 of a standardized pomegranate fruit extract containing 30% punicalagin in Wistar rats was >5 g/kg b.w.,
TumCCA↑, suppresses the growth of BC cells by arresting the cell cycle in the G0/G1 phase,
TumCMig↓, suppresses migration, invasion, and metastatic
TumCI↓,
TumMeta↓,
Apoptosis↑, stimulates apoptosis in MCF-7 cells via TGF-β/Smad3 signaling axis
TGF-β↓,
SMAD3↓,
CDK6↓, inhibits CDK6 that is important in cell cycle regulation,
PI3K↓, inhibits the PI3K/AKT pathway
Akt↓,
angioG↓,
VEGFR2↓, reduces VEGFR-2 tyrosine kinase activity
MAPK↓,
NEDD9↓, downregulated protein 9 (NEDD-9)
NF-kB↓, EA suppressed NF-κB precursor protein p105
eff↑, They showed that the encapsulation of EA in biodegradable polymeric nanoparticles would improve the bioavailability after oral administration and also enhance the anticancer properties
eff↑, Chitosan nanoparticles and EA with high anticancer efficacy could be a suitable therapeutic strategy
RadioS↑, showed that the synergistic effect of EA combined with radiotherapy/chemotherapy resulted in increased DNA damage and apoptosis as well as decreased levels of MGMT expression
ChemoSen↑,
DNAdam↑,
eff↑, combination of Paclitaxel and EA has shown promise in inhibiting tumor growth and metastasis in experimental BC models.
*toxicity∅, 630 mg/kg is the LD50 of EA in the rat population.
*toxicity∅, no-observed adverse effect level of EA is 2000 mg/kg body weight
HH↓,
Gli1↓, EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1.
GLI2↓,
CDK1/2/5/9↓,
p‑Akt↓,
NOTCH1↓,
Shh↓,
Snail↓,
E-cadherin↑,
NOTCH3↓,
HEY1↓,
TumCG↓, EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage.
TumCP↓,
Casp3↑,
cl‑PARP↑,
Bcl-2↓, EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
BAX↑,
COX2↓, EA inhibited the markers of angiogenesis (COX-2, HIF1α, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues.
Hif1a↓,
VEGF↓,
VEGFR2↓,
IL6↓,
IL8↓,
MMP2↓,
MMP9↓,
NA↓, EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways
Telomerase↓, EGCG stimulates telomere fragmentation through inhibiting telomerase activity.
DNMTs↓, EGCG reduced DNMTs,
cycD1/CCND1↓, EGCG also reduced the protein expression of cyclin D1, cyclin E, CDK2, CDK4, and CDK6. EGCG also inhibited the activity of CDK2 and CDK4, and caused Rb hypophosphorylation
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
HATs↓, EGCG can inhibit certain biomedically important molecular targets such as DNMTs, HATs, and HDACs
HDAC↓,
selectivity↑, EGCG has shown higher cytotoxicity in cancer cells than in their normal counterparts.
uPA↓, EGCG blocks urokinase, an enzyme which is essential for cancer growth and metastasis
NF-kB↓, EGCG inhibits NFκB and expression of TNF-α, reduces cancer promotion
TNF-α↓,
*ROS↓, It acts as strong ROS scavenger and antioxidant,
*antiOx↑,
Hif1a↓, ↓ HIF-1α; ↓ VEGF; ↓ VEGFR1;
VEGF↓,
MMP2↓, ↓ MMP-2; ↓ MMP-9; ↓ FAK;
MMP9↓,
FAK↓,
TIMP2↑, TIMP-2; ↑
Mcl-1↓, ↓ Mcl-1; ↓ survivin; ↓ XIAP
survivin↓,
XIAP↓,
PCNA↓, ↓ PCNA; ↑ 16; ↑ p18; ↑ p21; ↑ p27; ↑ pRb; ↑ p53; ↑ mdm2
p16↑,
P21↑,
p27↑,
pRB↑,
P53↑,
MDM2↑,
ROS↑, ↑ ROS; ↑ caspase-3; ↑ caspase-8; ↑ caspase-9; ↑ cytochrome c; ↑ Smac/DIABLO; ↓↑ Bax; Z Bak; ↓ cleaved PPAR;
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑,
Diablo↑,
BAX⇅,
cl‑PPARα↓,
PDGF↓, ↓ PDGF; ↓ PDGFRb; ↓ EGFR;
EGFR↓,
FOXO↑, activated FOXO transcription factors
AP-1↓, The inhibition of AP-1 activity by EGCG was associated with inhibition of JNK activation but not ERK activation.
JNK↓,
COX2↓, EGCG reduces the activity of COX-2 following interleukin-1A stimulation of human chondrocytes
angioG↓, EGCG inhibits angiogenesis by enhancing FOXO transcriptional activity
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
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TumCP↓, ferulic acid significantly inhibits the proliferation and migration of these cells
TumCMig↓,
TumCCA↑, ferulic acid significantly inhibits the proliferation and migration of these cells
Apoptosis↑,
ATM↑, ferulic acid activates the ATM/Chk2 and ATR/Chk1 pathways
Chk2↑,
ATR↑,
CHK1↑,
CK2↓, down regulating their relative cell cycle regulatory proteins (CDK2 and Cyclin A2 complex, CDK4/6 and Cyclin D1/E1 complex)
cycA1/CCNA1↑, Cyclin A2 complex
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
cycE/CCNE↓,
P53↑,
P21↑,
tyrosinase↓,
CK2↓,
TumCP↓,
TumCMig↓,
FGF↓,
FGFR1↓,
PI3K↓,
Akt↓,
VEGF↓,
FGFR1↓,
FGFR2↓,
PDGF↓,
ALAT↓,
AST↓,
TumCCA↑, G0/G1 phase arrest
CDK2↓,
CDK4↓,
CDK6↓,
BAX↓,
Bcl-2↓,
MMP2↓,
MMP9↓,
P53↑,
PARP↑,
PUMA↑,
NOXA↑,
Casp3↑,
Casp9↑,
TIMP1↑,
lipid-P↑,
mtDam↑,
EMT↓,
Vim↓,
E-cadherin↓,
p‑STAT3↓,
COX2↓,
CDC25↓,
RadioS↑,
ROS↑,
DNAdam↑,
γH2AX↑,
PTEN↑,
LC3II↓,
Beclin-1↓,
SOD↓,
Catalase↓,
GPx↓,
Fas↑,
*BioAv↓, ferulic acid stability and limited solubility in aqueous media continue to be key obstacles to its bioavailability, preclinical efficacy, and clinical use.
cMyc↓,
Beclin-1↑, ferulic acid by elevating the levels of the apoptosis and autophagy biomarkers, including beclin-1, Light chain (LC3-I/LC3-II), PTEN-induced putative kinase 1 (PINK-1), and Parkin
LC3‑Ⅱ/LC3‑Ⅰ↓,
*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
*p‑cMyc↑,
*NRF2↑,
*GSH↑,
*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
PI3K↓,
Akt↓,
TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
p27↑,
JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
MMP2↓,
MMP9↓,
uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
cFos↓,
cJun↓,
E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
Vim↓,
N-cadherin↓,
EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
Cyt‑c↑,
Diablo↑,
Casp↑,
cl‑PARP↑,
P53↑, fisetin with induction of p53 protein
COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
PGE2↓,
HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
HSP27↓,
DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
Casp3↑,
Casp9↑,
ROS↑, This was associated with production of intracellular ROS
AMPK↑, Fisetin induced AMPK signaling
NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
Ca+2↑,
mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
p70S6↓,
ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
IRE1↑,
ATF4↑,
GRP78/BiP↑,
eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer
half-life of 3.12 h.
NRF2↑, fisetin increased the protein level and accumulation Nrf2 and down regulated the protein levels of Keap1
Keap1↓,
ChemoSen↑, In vitro studies showed that fisetin and quercetin could also act against chemotherapeutic resistance in several cancers
BioAv↓, Fisetin has low aqueous solubility and bioavailability
Cyt‑c↑, release of cytochrome c from mitochondria, caspase-3 and caspase-9 mRNA and protein expression, and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels, were found to be regulated in the fisetin-treated cancer cell line
Casp3↑,
Casp9↑,
BAX↑,
tumCV↓, fisetin at 5–80 µM significantly reduced the viability of A431 human epidermoid carcinoma cells by the release of cytochrome c,
Mcl-1↓, reducing the anti-apoptotic protein expression of Bcl-2, Bcl-xL, and Mcl-1 along with elevation of pro-apoptotic protein expression (Bax, Bak, and Bad) and caspase cleavage and poly-ADP-ribose polymerase (PARP) protein
cl‑PARP↑,
IGF-1↓, fisetin promoted caspase-8 and cytochrome c expression, possibly by impeding the aberrant activation of insulin growth factor receptor 1 and Akt
Akt↓,
CDK6↓, fisetin binds with CDK6, which in turn blocks its activity with an inhibitory concentration (IC50) at a concentration of 0.85 μM
TumCCA↑, fisetin is identified as a regulator of cell cycle checkpoints, leading to cell arrest through CDK inhibition in HL60 cells and astrocyte cells over the G0/G1, S, and G2/M phases
P53?, exhibiting elevated levels of p53
cycD1/CCND1↓, 10–60 μM fisetin concentration, prostate cancer cells PC3, LNCaP, and CWR22Ry1 had decreased cellular viability and decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
cycE/CCNE↓,
CDK2↓, decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
CDK4↓,
CDK6↓,
MMP2↓, fisetin displayed tumor inhibitory effects by blocking MMP-2 and MMP-9 at mRNA and protein levels in prostate PC-3 cells
MMP9↓,
MMP1↓, Similarly, fisetin can also inhibit MMP-1, MMP-9, MMP-7, MMP-3, and MMP-14 gene expression linked with ECM remodeling in human umbilical vascular endothelial cells (HUVECs) and HT-1080 fibrosarcoma cells [9
MMP7↓,
MMP3↓,
VEGF↓, fisetin in a concentration-dependent manner (10–50 μM concentration) significantly inhibited regular serum, growth-enhancing supplement, and vascular endothelial growth factor (VEGF)
PI3K↓, fisetin inhibited PI3K expression and phosphorylation of Akt
mTOR↓, fisetin treatment activated the apoptotic process through inhibiting both PI3K and mammalian target of rapamycin (mTOR) signaling pathways
COX2↓, fisetin resulted in activation of apoptosis and inhibition of COX-2 and the Wnt/EGFR/NF-kB pathway
Wnt↓,
EGFR↓,
NF-kB↓,
ERK↓, Fisetin is one of the flavonoids that has been found to suppress ERK1/2 signaling in human gastric (SGC7901), hepatic (HepG2), colorectal (Caco-2)
ROS↑, fisetin induced ROS generation and suppressed ERK through its phosphorylation
angioG↓, fisetin-induced anti-angiogenesis led to reduced VEGF and epidermal growth factor receptor (EGFR) expression
TNF-α↓, Fisetin suppressed IL-1β-mediated expression of inducible nitric oxide synthase, nitric oxide, interleukin-6, tumor necrotic factor-α, prostaglandin E2, cyclooxygenase-2 (iNOS, NO, IL-6, TNF-α, PGE2, and COX-2),
PGE2↓,
iNOS↓,
NO↓,
IL6↓,
HSP70/HSPA5↝, fisetin-mediated inhibition of cellular proliferation by HSP70 and HSP27 regulation
HSP27↝,
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↓,
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*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and
poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia-
related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells
by downregulating the steroid receptor coactivator, Twist1
and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer
cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in
neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp↓, The expres-
sion of P-gp at mRNA and protein levels is reduced in HNK
treatment on human MDR and MCF-7/ADR breast cancer cell
lines
EZH2↓, Human prostate cancer DU145 and PC-3 cells, which possess high constitutive EZH2 expression, were treated with 5-20 µM luteolin at various times significantly inhibited EZH2
cycD1/CCND1↓, Mechanistic investigations revealed that miR-26a overexpression suppressed cell cycle regulatory molecules such as cyclin D and E, cyclin dependent kinases CDK4 and CDK6
cycE/CCNE↓,
CDK4↓,
CDK6↓,
ChemoSen↑, Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects
RadioS↑,
Imm↑,
*AntiDiabetic↑, Metformin, the preferred glucose-lowering drug for patients with T2DM, is typically an adenosine monophosphate-activated protein kinase (AMPK) activator
*AMPK↑,
TumCP↓, AMPK restores the normal function of the liver and other tissues in diabetic patients as well as stops the metabolism of rapidly proliferating tumors
hepatoP↑,
ATP↓, . This leads to a decrease in intracellular ATP and an increase in AMP levels, which inhibits gluconeogenesis and further activates AMPK.
AMP↑,
glucoNG↓,
ROS↑, metformin can also promote reactive oxygen species (ROS) production by inhibiting mitochondrial respiratory-chain complex I, which can lead to DNA damage and gene mutation [23]
compI↓,
DNAdam↑,
CSCs↓, The advantage of metformin combined with chemotherapy is related to killing cancer stem cells [30].
NP/CIPN↓, metformin could improve the adverse effects of neuropathy (PN) in paclitaxel-treated breast cancer patients
chemoP↑, Thus, metformin may be able to be used as a chemoprotective agent, reducing the toxicity of chemotherapy and ameliorating adverse effects.
toxicity↓, The safety and tolerability of metformin were confirmed, but a large number of phase III clinical trials are still needed to follow up the study
Trx↓, Metformin radiosensitizes ductal breast cancer MCF7 cells by increasing intracellular reactive oxygen species (ROS) production through decreased thioredoxin (Trx) expression
eff↑, In addition, metformin may act in combination with the aspirin metabolite salicylic acid to enhance the proliferation inhibition of radiotherapy on prostate cancer
cycD1/CCND1↓, addition of metformin reduced the expression levels of cyclin D1, CDK4, CDK6, cyclin E, and CDK2 in gastric cancer cells
CDK4↓,
CDK6↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓, CAPE also induces G1 phase cell arrest by lowering the expression of CDK4, CDK6, Rb, and p-Rb. M
CDK6↓,
pRB↓,
ROS↓, Artepillin C, a bioactive component of Brazilian green propolis, reduces oxidative damage markers, namely 4-HNE-modified proteins, 8-OHdG, malonaldehyde, and thiobarbituric acid reactive substances in lung tissues with pulmonary adenocarcinoma
TumCCA↑, Propolin, a novel component of prenylflavanones in Taiwanese propolis, was demonstrated to have anti-cancer properties. Propolin H induces cell arrest at G1 phase and upregulates the expression of p21
P21↑,
PI3K↓, Propolin C also inhibits PI3K/Akt and ERK-mediated epithelial-to-mesenchymal transition by upregulating E-cadherin (epithelial cell marker) and downregulating vimentin
Akt↓,
EMT↓,
E-cadherin↑,
Vim↓,
*COX2↓, bioactive compounds such as CAPE, galangin significantly reduce the activity of lung cyclooxygenase (COX) and myeloperoxidase (MPO), and malonaldehyde (MDA), TNF-α, and IL-6 levels, while increasing the activity of catalase (CAT) and SOD
*MPO↓,
*MDA↓,
*TNF-α↓,
*IL6↓,
*Catalase↑,
*SOD↑,
*AST↓, Chrysin also reduces the expression of oxidative and inflammatory markers such as aspartate transaminase (AST), alanine aminotransferase (ALT), IL-1β, IL-10, TNF-α, and MDA levels and increases the antioxidant parameters such as SOD, CAT, and GPx
*ALAT↓,
*IL1β↓,
*IL10↓,
*GPx↓,
*TLR4↓, propolis also inhibits the expression of Toll-like receptor 4 (TLR4), macrophage infiltration, MPO activity, and apoptosis of lung tissues in septic animals
*Sepsis↓,
*IFN-γ↑, CAPE also significantly increases IFN-γ
*GSH↑, propolis significantly increased the level of GSH and the histological appearances of propolis-treated bleomycin-induced pulmonary fibrosis rats.
*NRF2↑, CAPE significantly increases the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2)
*α-SMA↓, propolis significantly inhibits the expression of α- SMA, collagen fibers, and TGF-1β.
*TGF-β↓,
*IL5↓, Propolis also inhibits the expression of inflammatory cytokines and chemokines such as TNF-α, IL-5, IL-6, IL-8, IL-10, NF-kB, IFN-γ, PGF2a, and PGE2.
*IL6↓,
*IL8↓,
*PGE2↓,
*NF-kB↓,
*MMP9↓, downregulating the expression of TGF-1β, ICAM-1, α-SMA, MMP-9, IgE, and IgG1.
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,
ROS↑, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cycD
GSH↓, reduced glutathione (GSH) levels in mouse colon cancer cells
DNAdam↑,
ChemoSen↑, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy
RadioS↑, piperlongumine treatment enhances ROS production via decreasing GSH levels and causing thioredoxin reductase inhibition
BioEnh↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine
selectivity↑, It shows selectivity toward human cancer cells over normal cells and has minimal side effects
BioAv↓, ts low aqueous solubility affects its anti-cancer activity by limiting its bioavailability during oral administration
eff↑, encapsulation of piperlongumine in another biocompatible natural polymer, chitosan, has been found to result in pH-dependent piperlongumine release and to enhance cytotoxicity via efficient intracellular ROS accumulation against human gastric carcin
p‑Akt↓, Fig 2
mTOR↓,
GSK‐3β↓,
β-catenin/ZEB1↓,
HK2↓, iperlongumine treatment decreases cell proliferation, single-cell colony-formation ability, and HK2-mediated glycolysis in NSCLC cells via inhibiting the interaction between HK2 and voltage-dependent anion channel 1 (VDAC1)
Glycolysis↓,
Cyt‑c↑,
Casp9↑,
Casp3↑,
Casp7↑,
cl‑PARP↑,
TrxR↓, piperlongumine (4 or 12 mg/kg/day for 15 days) administration significantly inhibits increase in
tumor weight and volume with less TrxR1 activity in SGC-7901 cell
ER Stress↑,
ATF4↝,
CHOP↑, activating the downstream ER-MAPK-C/EBP homologous protein (CHOP) signaling pathway
Prx4↑, piperlongumine kills high-grade glioma cells via oxidative inactivation of PRDX4 mediated ROS induction, thereby inducing intracellular ER stress
NF-kB↓, piperlongumine treatment (2.5â5 mg/ kg body weight) decreases the growth of lung tumors via inhibition of NF-κB
cycD1/CCND1↓, decreases expression of cyclin D1, cyclin- dependent kinase (CDK)-4, CDK-6, p- retinoblastoma (p-Rb)
CDK4↓,
CDK6↓,
p‑RB1↓,
RAS↓, piperlongumine downregulates the expression of Ras protein
cMyc↓, inhibiting the activity of other related proteins, such as Akt/NF-κB, c-Myc, and cyclin D1 in DMH + DSS induced colon
tumor cells
TumCCA↑, by arresting colon tumor cells in the G2/M phase of the cell cycle
selectivity↑, hows more selective cytotoxicity against human breast cancer MCF-7
cells than human breast epithelial MCF-10A cells
STAT3↓, thus inducing inhibition of the STAT3 signaling pathway in multiple myeloma cells
NRF2↑, Nrf2) activation has been found to mediate the upregulation of heme oxygenase-1 (HO-1) in piperlongumine treated MCF-7 and MCF-10A cells
HO-1↑,
PTEN↑, stimulates ROS accumulation; p53, p27, and
PTEN overexpression
P-gp↓, P-gp, MDR1, MRP1, survivin, p-Akt, NF-κB, and Twist downregulation;
MDR1↓,
MRP1↓,
survivin↓,
Twist↓,
AP-1↓, iperlongumine significantly suppresses the expression of transcription factors, such as AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6, and YY1.
Sp1/3/4↓,
STAT1↓,
STAT6↓,
SOX4↑, increased expression of p21, SOX4, and XBP in B-ALL cells
XBP-1↑,
P21↑,
eff↑, combined use of piperlongumine with cisplatin enhances the sensitivity toward cisplatin by inhibiting
Akt phosphorylation
Inflam↓, inflammation (COX-2, IL6); invasion and metastasis, such as ICAM-1, MMP-9, CXCR-4, VEGF;
COX2↓,
IL6↓,
MMP9↓,
TumMeta↓,
TumCI↓,
ICAM-1↓,
CXCR4↓,
VEGF↓,
angioG↓,
Half-Life↝, The analysis of the plasma of piperlongumine treated mice (50 mg/kg) after intraperitoneal administration, 1511.9 ng/ml, 418.2 ng/ml, and 41.9 ng/ml concentrations ofplasma piperlongumine were found at 30 minutes, 3 hours, and 24 hours, respecti
BioAv↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine
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↑,
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
*Inflam↓, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties.
*antiOx↑,
*AntiCan↑,
Casp3↓, Quercetin increases apoptosis and autophagy in cancer by activating caspase-3, inhibiting the phosphorylation of Akt, mTOR, and ERK, lessening β-catenin, and stabilizing the stabilization of HIF-1α.
p‑Akt↓,
p‑mTOR↓,
p‑ERK↓,
β-catenin/ZEB1↓,
Hif1a↓,
AntiAg↓, Quercetin have revealed an anti-tumor effect by reducing development of blood vessels. I
VEGFR2↓, decrease tumor growth through targeting VEGFR-2-mediated angiogenesis pathway and suppressing the downstream regulatory component AKT in prostate and breast malignancies.
EMT↓, effects of quercetin on inhibition of EMT, angiogenesis, and invasiveness through the epidermal growth factor receptor (EGFR)/VEGFR-2-mediated pathway in breast cancer
EGFR↓,
MMP2↓, MMP2 and MMP9 are two remarkable compounds in metastatic breast cancer (28–30). quercetin on breast cancer cell lines (MDA-MB-231) and showed that after treatment with this flavonoid, the expression of these two proteinases decreased
MMP↓,
TumMeta↓, head and neck (HNSCC), the inhibitory effect of quercetin on the migration of tumor cells has been shown by regulating the expression of MMPs
MMPs↓,
Akt↓, quercetin by inhibiting the Akt activation pathway dependent on Snail, diminishing the expression of N-cadherin, vimentin, and ADAM9 and raising the expression of E-cadherin and proteins
Snail↓,
N-cadherin↓,
Vim↓,
E-cadherin↑,
STAT3↓, inhibiting STAT3 signaling
TGF-β↓, reducing the expression of TGF-β caused by vimentin and N-cadherin, Twist, Snail, and Slug and increasing the expression of E-cadherin in PC-3 cells.
ROS↓, quercetin exerted an anti-proliferative role on HCC cells by lessening intracellular ROS independently of p53 expression
P53↑, increasing the expression of p53 and BAX in hepatocellular carcinoma (HepG2) cell lines through the reduction of PKC, PI3K, and cyclooxygenase (COX-2)
BAX↑,
PKCδ↓,
PI3K↓,
COX2↓,
cFLIP↓, quercetin by inhibiting PI3K/AKT/mTOR and STAT3 pathways, decreasing the expression of cellular proteins such as c-FLIP, cyclin D1, and c-Myc, as well as reducing the production of IL-6 and IL-10 cytokines, leads to the death of PEL cells
cycD1/CCND1↓,
cMyc↓,
IL6↓,
IL10↓,
Cyt‑c↑, In addition, quercetin induced c-cytochrome-dependent apoptosis and caspase-3 almost exclusively in the HSB2 cell line
TumCCA↑, Exposure of K562 cells to quercetin also significantly raised the cells in the G2/M phase, which reached a maximum peak in 24 hours
DNMTs↓, pathway through DNA demethylation activity, histone deacetylase (HDAC) repression, and H3ac and H4ac enrichment
HDAC↓,
ac‑H3↑,
ac‑H4↑,
Diablo↑, SMAC/DIABLO exhibited activation
Casp3↑, enhanced levels of activated caspase 3, cleaved caspase 9, and PARP1
Casp9↑,
PARP1↑,
eff↑, green tea and quercetin as monotherapy caused the reduction of levels of anti-apoptotic proteins, CDK6, CDK2, CYCLIN D/E/A, BCL-2, BCL-XL, and MCL-1 and an increase in expression of BAX.
PTEN↑, Quercetin upregulates the level of PTEN as a tumor suppressor, which inhibits AKT signaling
VEGF↓, Quercetin had anti-inflammatory and anti-angiogenesis effects, decreasing VGEF-A, NO, iNOS, and COX-2 levels
NO↓,
iNOS↓,
ChemoSen↑, quercetin and chemotherapy can potentiate their effect on the malignant cell
eff↑, combination with hyperthermia, Shen et al. Quercetin is a method used in cancer treatment by heating, and it was found to reduce Doxorubicin hydrochloride resistance in leukemia cell line K562
eff↑, treatment with ellagic acid, luteolin, and curcumin alone showed excellent anticancer effects.
eff↑, co-treatment with quercetin and curcumin led to a reduction of mitochondrial membrane integrity, promotion of cytochrome C release, and apoptosis induction in CML cells
uPA↓, A-549 cells were shown to have reduced mRNA expressions of urokinase plasminogen activator (uPA), Upar, protein expression of CXCR-4, CXCL-12, SDF-1 when quercetin was applied at 20 and 40 mM/ml by real-time PCR.
CXCR4↓,
CXCL12↓,
CLDN2↓, A-549 cells, indicated that quercetin could reduce mRNA and protein expression of Claudin-2 in A-549 cell lines without involving Akt and ERK1/2,
CDK6↓, CDK6, which supports the growth and viability of various cancer cells, was hampered by the dose-dependent manner of quercetin (IC50 dose of QR for A-549 cells is 52.35 ± 2.44 μM).
MMP9↓, quercetin up-regulated the rates of G1 phase cell cycle and cellular apoptotic in both examined cell lines compared with the control group, while it declined the expressions of the PI3K, AKT, MMP-2, and MMP-9 proteins
TSP-1↑, quercetin increased TSP-1 mRNA and protein expression to inhibit angiogenesis,
Ki-67↓, significant reductions in Ki67 and PCNA proliferation markers and cell survival markers in response to quercetin and/or resveratrol.
PCNA↓,
ROS↑, Also, quercetin effectively causes intracellular ROS production and ER stress
ER Stress↑,
| - |
in-vitro, |
BC, |
MCF-7 |
|
|
|
- |
in-vitro, |
Lung, |
A549 |
|
|
|
CDK6↓, The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6.
tumCV↓, Quercetin also decreases the viability and colony formation potential of selected cancer cells.
Apoptosis↑, Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression
ROS↓,
eff↑, Interestingly, when used in combination, quercetin increases the efficiencies of other anticancer molecules like losartan, paclitaxel, and resveratrol in different cancers
*Inflam↓, Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
*antiOx↑,
*AntiAg↑,
*chemoPv↑, Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis
ChemoSen↑,
BioAv↑, Compared to other known polyphenols, such as quercetin and catechin, trans-resveratrol is well absorbed much more efficiently following oral administration to humans
Half-Life↝, Compared to resveratrol, which has a plasma half-life of 8–14 min, the metabolites have a plasma half-life of about 9.2 hours
COX2↓, there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed
cycD1/CCND1↓, Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
MMP9↓, associated with decreased COX-2 and matrix metalloprotease-9 expression and suppression of NFκB activation
NF-kB↓,
Telomerase↓, Relatively high concentrations also substantially downregulate telomerase activity
PSA↓, Resveratrol downregulates PSA by a mechanism independent of changes in AR
MAPK↑, Resveratrol treatment of various prostate cells also accompanied the activation of MAPK signaling and an increase in cellular p53
P53↑,
Dose↝, Most clinical trials utilize doses of GFN ranging from 25 to 800 μmol , translating to about 65–2105 g raw broccoli or 3/4 to 23 cups of raw broccoli.
eff↝, SFN-rich powders have been made by drying out broccoli sprout
IL1β↓,
IL6↓,
IL12↓,
TNF-α↓,
COX2↓,
CXCR4↓,
MPO↓,
HSP70/HSPA5↓,
HSP90↓,
VCAM-1↓,
IKKα↓,
NF-kB↓,
HO-1↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Diablo↑,
CHOP↑,
survivin↓,
XIAP↓,
p38↑,
Fas↑,
PUMA↑,
VEGF↓,
Hif1a↓,
Twist↓,
Zeb1↓,
Vim↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Snail↓,
CD44↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDK4↓,
CDK6↓,
p50↓,
P53↑,
P21↑,
GSH↑,
SOD↑,
GSTs↑,
mTOR↓,
Akt↓,
PI3K↓,
β-catenin/ZEB1↓,
IGF-1↓,
cMyc↓,
CSCs↓, Inhibited TS-induced, CSC-like properties
ROS⇅, It appears that the cellular and/or physiological context(s)
determines whether TQ acts as a pro-oxidant or an anti-ox-
idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in
different cancer cells have been observed with 5-fluorouracil
in gastric cancer and colorectal cancer models
Showing Research Papers: 1 to 35 of 35
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 35
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned ⓘ
NA↓, 1,
Redox & Oxidative Stress ⓘ
antiOx↓, 1, Catalase↓, 1, compI↓, 1, GPx↓, 1, GSH↓, 3, GSH↑, 1, GSTs↑, 2, HO-1↓, 3, HO-1↑, 3, HO-2↓, 1, Keap1↓, 1, lipid-P↑, 1, MAD↓, 1, MDA↑, 1, MPO↓, 1, NADH↓, 1, NQO1↑, 1, NRF2↓, 1, NRF2↑, 3, Prx4↑, 1, PYCR1↓, 1, ROS↓, 5, ROS↑, 18, ROS⇅, 1, SOD↓, 3, SOD↑, 2, SOD1↑, 1, SOD2↑, 1, Trx↓, 1, TrxR↓, 2,
Mitochondria & Bioenergetics ⓘ
AIF↑, 4, ATP↓, 2, CDC2↓, 1, CDC25↓, 3, FGFR1↓, 3, MMP↓, 11, mtDam↑, 4, OCR↓, 1, OCR↑, 1, XIAP↓, 6,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AMP↑, 1, AMPK↑, 4, ATG7↑, 1, CAIX↓, 1, cMyc↓, 10, ECAR↓, 1, ECAR↝, 1, glucoNG↓, 1, GlucoseCon↓, 2, Glycolysis↓, 5, H2S↑, 1, HK2↓, 2, lactateProd↓, 2, LDH↓, 2, NADPH↑, 1, PDH↝, 1, PDK1?, 2, PKM2↓, 2, cl‑PPARα↓, 1, PPARγ↑, 2, SIRT1↓, 3,
Cell Death ⓘ
Akt↓, 16, Akt↑, 1, p‑Akt↓, 5, Apoptosis↑, 15, Bak↑, 2, BAX↓, 1, BAX↑, 11, BAX⇅, 1, Bax:Bcl2↑, 4, Bcl-2↓, 13, Bcl-xL↓, 4, BID↓, 1, BID↑, 2, BIM↑, 2, Casp↑, 3, Casp12↑, 1, Casp3↓, 1, Casp3↑, 18, Casp7↑, 3, Casp8↑, 5, Casp9↑, 13, cFLIP↓, 2, Chk2↑, 1, CK2↓, 3, Cyt‑c↑, 15, Diablo↑, 6, DR4↑, 1, DR5↑, 3, FADD↑, 1, Fas↑, 5, HEY1↓, 1, IAP1↓, 1, iNOS↓, 4, JNK↓, 1, JNK↑, 5, MAPK↓, 4, MAPK↑, 2, Mcl-1↓, 6, MDM2↓, 2, MDM2↑, 1, Myc↓, 2, NOXA↑, 2, p27↑, 8, p38↑, 4, PUMA↑, 3, survivin↓, 8, Telomerase↓, 4, TRAIL↑, 1, TRPV1↑, 1, TumCD↑, 1,
Kinase & Signal Transduction ⓘ
HER2/EBBR2↓, 1, p‑HER2/EBBR2↓, 1, p70S6↓, 1, Sp1/3/4↓, 3,
Transcription & Epigenetics ⓘ
cJun↓, 2, EZH2↓, 1, ac‑H3↑, 1, ac‑H4↑, 1, HATs↓, 1, miR-27a-3p↓, 2, pRB↓, 2, pRB↑, 1, tumCV↓, 6,
Protein Folding & ER Stress ⓘ
CHOP↑, 4, eIF2α↓, 1, p‑eIF2α↑, 1, ER Stress↑, 7, GRP78/BiP↑, 4, HSF1↓, 1, HSP27↓, 1, HSP27↝, 1, HSP70/HSPA5↓, 3, HSP70/HSPA5↑, 1, HSP70/HSPA5↝, 1, HSP90↓, 2, IRE1↑, 2, XBP-1↑, 1,
Autophagy & Lysosomes ⓘ
Beclin-1↓, 1, Beclin-1↑, 3, LC3‑Ⅱ/LC3‑Ⅰ↓, 1, LC3II↓, 1, LC3II↑, 3, p62↑, 1, TumAuto↑, 2,
DNA Damage & Repair ⓘ
ATM↑, 1, ATR↑, 1, CHK1↑, 1, CYP1B1↑, 1, DNAdam↓, 1, DNAdam↑, 8, DNMT1↓, 1, DNMTs↓, 2, p16↑, 2, P53?, 1, P53↑, 15, p‑P53↑, 1, PARP↑, 2, cl‑PARP↑, 11, PARP1↓, 1, PARP1↑, 1, PCNA↓, 4, SIRT6↑, 1, UHRF1↓, 1, γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK1↓, 1, CDK1/2/5/9↓, 1, CDK2↓, 18, CDK2↑, 1, CDK4↓, 27, cycA1/CCNA1↓, 2, cycA1/CCNA1↑, 1, CycB/CCNB1↓, 2, CycB/CCNB1↑, 1, cycD1/CCND1↓, 28, CycD3↓, 1, cycE/CCNE↓, 14, cycE1↓, 1, E2Fs↓, 1, P21↑, 16, RB1↓, 1, p‑RB1↓, 2, TumCCA↑, 21,
Proliferation, Differentiation & Cell State ⓘ
CD44↓, 1, CDK8↓, 1, cFos↓, 3, CIP2A↓, 1, cMET↓, 2, CSCs↓, 3, EMT↓, 9, ERK↓, 3, ERK↑, 1, p‑ERK↓, 2, FGF↓, 1, FGFR2↓, 1, FOXM1↓, 1, FOXO↑, 2, FOXO3↑, 1, p‑FOXO3↓, 1, Gli↓, 1, Gli1↓, 1, GSK‐3β↓, 2, HDAC↓, 3, HDAC1↓, 2, HDAC3↓, 1, HH↓, 2, IGF-1↓, 3, Let-7↑, 1, miR-34a↑, 3, mTOR↓, 9, p‑mTOR↓, 1, mTORC1↓, 1, Nanog↓, 1, NOTCH↓, 4, NOTCH1↓, 1, NOTCH3↓, 1, OCT4↓, 1, P70S6K↓, 1, PI3K↓, 15, PTEN↑, 4, RAS↓, 2, Shh↓, 1, SOX2↓, 1, STAT1↓, 1, STAT3↓, 7, p‑STAT3↓, 3, STAT6↓, 2, TCF-4↓, 1, TOP1↓, 1, TOP2↓, 2, TumCG↓, 6, tyrosinase↓, 1, Wnt↓, 3, Wnt/(β-catenin)↓, 2,
Migration ⓘ
5LO↓, 2, AntiAg↓, 1, AP-1↓, 4, ATPase↓, 1, AXL↓, 1, Ca+2↑, 8, Ca+2↝, 1, CAFs/TAFs↓, 1, CLDN2↓, 1, CXCL12↓, 1, DLC1↑, 1, E-cadherin↓, 1, E-cadherin↑, 10, FAK↓, 2, p‑FAK↓, 1, GLI2↓, 1, ITGA5↓, 1, Ki-67↓, 5, miR-200b↑, 1, MMP1↓, 1, MMP2↓, 13, MMP3↓, 1, MMP7↓, 3, MMP9↓, 17, MMPs↓, 1, N-cadherin↓, 5, NEDD9↓, 1, PDGF↓, 2, PKCδ↓, 3, Rho↑, 1, ROCK1↑, 1, Slug↓, 3, SMAD3↓, 2, Snail?, 1, Snail↓, 7, SOX4↑, 1, TGF-β↓, 5, TGF-β↑, 1, TIMP1↑, 1, TIMP2↑, 1, TSP-1↑, 1, TumCI↓, 5, TumCMig↓, 4, TumCMig↑, 1, TumCP↓, 11, TumCP↑, 1, TumMeta↓, 8, Twist↓, 9, uPA↓, 6, VCAM-1↓, 1, Vim↓, 10, Zeb1↓, 3, ZEB2↓, 1, β-catenin/ZEB1↓, 8,
Angiogenesis & Vasculature ⓘ
angioG↓, 12, ATF4↑, 3, ATF4↝, 1, EGFR↓, 5, Endoglin↑, 1, HIF-1↓, 1, Hif1a↓, 10, NO↓, 2, NO↑, 1, VEGF↓, 15, VEGFR2↓, 6,
Barriers & Transport ⓘ
GLUT1↓, 3, NHE1↓, 1, P-gp↓, 2,
Immune & Inflammatory Signaling ⓘ
COX1↓, 1, COX2↓, 15, CXCL1↓, 1, CXCR4↓, 5, ICAM-1↓, 1, IKKα↓, 2, IL1↓, 1, IL10↓, 2, IL12↓, 2, IL1β↓, 1, IL2↑, 1, IL4↓, 1, IL6↓, 8, IL8↓, 3, Imm↑, 1, Inflam↓, 3, JAK↓, 1, JAK1↓, 1, JAK2↓, 3, M2 MC↓, 1, NF-kB↓, 17, NF-kB↑, 1, p50↓, 1, p65↓, 1, PD-1↓, 1, PD-L1↓, 1, PGE2↓, 3, PSA↓, 1, TNF-α↓, 4,
Hormonal & Nuclear Receptors ⓘ
CDK6↓, 37,
Drug Metabolism & Resistance ⓘ
BioAv↓, 2, BioAv↑, 3, BioEnh↑, 2, ChemoSen↑, 15, Dose↝, 2, Dose∅, 1, eff↓, 1, eff↑, 24, eff↝, 2, Half-Life↝, 3, MDR1↓, 1, MRP1↓, 1, RadioS↑, 11, selectivity↑, 8, TET2↑, 1,
Clinical Biomarkers ⓘ
ALAT↓, 1, AST↓, 1, BMPs↑, 1, EGFR↓, 5, EZH2↓, 1, FOXM1↓, 1, HER2/EBBR2↓, 1, p‑HER2/EBBR2↓, 1, IL6↓, 8, Ki-67↓, 5, LDH↓, 2, Myc↓, 2, PD-L1↓, 1, PSA↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 4, cardioP↑, 1, chemoP↑, 1, chemoPv↑, 3, ChemoSideEff↓, 2, hepatoP↑, 1, NP/CIPN↓, 1, toxicity↓, 2, TumW↓, 2,
Total Targets: 372
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 6, Catalase↑, 1, GPx↓, 1, GSH↑, 3, HO-1↑, 1, Keap1↑, 1, lipid-P↓, 1, MDA↓, 1, MPO↓, 1, NRF2↑, 4, ROS↓, 3, SIRT3↑, 1, SOD↑, 1,
Mitochondria & Bioenergetics ⓘ
PGC-1α↑, 1,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AMPK↑, 1, p‑cMyc↑, 1, PPARγ↑, 1,
Cell Death ⓘ
Casp3↓, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↓, 1, ERK↑, 1,
Migration ⓘ
AntiAg↑, 2, MMP9↓, 1, Rho↓, 1, TGF-β↓, 1, α-SMA↓, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, IFN-γ↑, 1, IL10↓, 1, IL1β↓, 1, IL5↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 5, NF-kB↓, 2, PGE2↓, 1, TLR4↓, 1, TNF-α↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 4,
Clinical Biomarkers ⓘ
ALAT↓, 1, AST↓, 1, GutMicro↑, 1, IL6↓, 2,
Functional Outcomes ⓘ
AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 1, chemoP↑, 1, chemoPv↑, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 1, Obesity↓, 1, toxicity∅, 3,
Infection & Microbiome ⓘ
Sepsis↓, 1,
Total Targets: 57
Scientific Paper Hit Count for: CDK6, Cyclin-dependent kinase 6
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#:895 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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