Fisetin / Bcl-2 Cancer Research Results

FIS, Fisetin: Click to Expand ⟱
Features:
Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes.

-Note half-life 3-4hrs
- Oral BioAv low (40-50%)
Pathways:
- induce ROS production in cancer cells, but also known to reduce it.
Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells
Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Does not appear to lower antioxidants in cancer cells
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CD133↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Fisetin effect on Cancer Cells
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR signaling ↔ adaptive suppression Driver Loss of survival and growth signaling Fisetin consistently suppresses pro-survival PI3K/AKT signaling, supporting growth inhibition and sensitization to stress
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of inflammatory survival transcription NF-κB inhibition contributes to anti-inflammatory effects and reduced tumor-supportive signaling
3 Reactive oxygen species (ROS) ↑ ROS (context- & dose-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Fisetin can act as a pro-oxidant in cancer cells at higher stress/dose while remaining antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of intrinsic apoptosis Mitochondrial apoptosis occurs downstream of signaling and redox disruption
5 Cell cycle regulation ↑ G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream pathway inhibition rather than direct CDK blockade
6 Senescence / senolytic action ↑ senescence clearance (senescent-like tumor/stroma subsets) ↓ senescent cell burden (selective) Secondary Selective vulnerability of senescent-like cells Fisetin is commonly described as senolytic; in cancer context this may impact tumor microenvironment and therapy-induced senescence
7 MAPK stress signaling (JNK / p38) ↑ JNK / ↑ p38 (context-dependent) ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation often follows ROS increase and supports apoptotic signaling
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 activation reflects redox buffering responses rather than primary cytotoxicity
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT and protease activity limit invasive behavior downstream of signaling changes


Bcl-2, B-cell CLL/lymphoma 2: Click to Expand ⟱
Source: HalifaxProj (inhibit) CGL-Driver Genes
Type: Antiapoptotic Oncogene
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.
Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.
Scientific Papers found: Click to Expand⟱
2849- FIS,    Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
- in-vitro, Melanoma, U266
TumCD↑, TumCCA↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, p‑Akt↓, p‑mTOR↓, ROS↑, eff↓,
2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, p38↓, *antiOx↑, *neuroP↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, DNAdam↑, MMP↓, eff↑, ROS↑, cl‑PARP↑, Cyt‑c↑, Diablo↑, P53↑, p65↓, Myc↓, HSP70/HSPA5↓, HSP27↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, TumCCA↑, CDK2↓, CDK4↓, cycD1/CCND1↓, cycA1/CCNA1↓, P21↑, MMP2↓, MMP9↓, TumMeta↓, MMP1↓, MMP3↓, MMP7↓, MET↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↑, uPA↓, ChemoSen↑, EMT↓, Twist↓, Zeb1↓, cFos↓, cJun↓, EGF↓, angioG↓, VEGF↓, eNOS↓, *NRF2↑, HO-1↑, NRF2↓, GSTs↓, ATF4↓,
2856- FIS,    N -acetyl- L -cysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells
- in-vitro, Colon, COLO205
eff↑, ROS↑, tumCV↓, Casp3↑, Bcl-2↓, MMP↓, eff↑,
2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
COX2↓, PGE2↓, EGFR↓, Wnt↓, β-catenin/ZEB1↓, TCF↑, Apoptosis↑, Casp3↑, cl‑PARP↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, Akt↓, mTOR↓, ACC↑, Cyt‑c↑, Diablo↑, cl‑Casp8↑, Fas↑, DR5↑, TRAIL↑, Securin↓, CDC2↓, CDC25↓, HSP70/HSPA5↓, CDK2↓, CDK4↓, cycD1/CCND1↓, MMP2↓, uPA↓, NF-kB↓, cFos↓, cJun↓, MEK↓, p‑ERK↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↓, NF-kB↑, ROS↑, DNAdam↑, MMP↓, CHOP↑, eff↑, ChemoSen↑,
2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
*antiOx↑, *Inflam↓, neuroP↑, hepatoP↑, RenoP↑, cycD1/CCND1↓, TumCCA↑, MMPs↓, VEGF↓, MAPK↓, NF-kB↓, angioG↓, Beclin-1↑, LC3s↑, ATG5↑, Bcl-2↓, BAX↑, Casp↑, TNF-α↓, Half-Life↓, MMP↓, mt-ROS↑, cl‑PARP↑, CDK2↓, CDK4↓, Cyt‑c↑, Diablo↑, DR5↑, Fas↑, PCNA↓, Ki-67↓, p‑H3↓, chemoP↑, Ca+2↑, Dose↝, CDC25↓, CDC2↓, CHK1↑, Chk2↑, ATM↑, PCK1↓, RAS↓, p‑p38↓, Rho↓, uPA↓, MMP7↓, MMP13↓, GSK‐3β↑, E-cadherin↑, survivin↓, VEGFR2↓, IAP2↓, STAT3↓, JAK1↓, mTORC1↓, mTORC2↓, NRF2↑,
2828- FIS,    Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review
- Review, Var, NA
*neuroP↑, *antiOx↑, *Inflam↓, RenoP↑, COX2↓, Wnt↓, EGFR↓, NF-kB↓, Casp3↑, Ca+2↑, Casp8↑, TumCCA↑, CDK1↓, PI3K↓, Akt↓, mTOR↓, MAPK↓, *P53↓, *P21↓, *p16↓, mTORC1↓, mTORC2↓, P53↑, P21↑, cycD1/CCND1↓, cycA1/CCNA1↓, CDK2↓, CDK4↓, BAX↑, Bcl-2↓, PCNA↓, HER2/EBBR2↓, Cyt‑c↑, MMP↓, cl‑Casp9↑, MMP2↓, MMP9↓, cl‑PARP↑, uPA↓, DR4↑, DR5↑, ROS↓, AIF↑, CDC25↓, Dose↑, CHOP↑, ROS↑, cMyc↓, cardioP↑,
2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, mtDam↑, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, Bak↑, BIM↑, Bcl-xL↓, Bcl-2↓, P53↑, ROS↑, AMPK↑, Casp9↑, Casp3↑, BID↑, AIF↑, Akt↓, mTOR↓, MAPK↓, Wnt↓, β-catenin/ZEB1↓, TumCCA↑, P21↑, p27↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, TumMeta↓, uPA↓, E-cadherin↑, Vim↓, EMT↓, Twist↓, DNAdam↑, ROS↓, COX2↓, PGE2↓, HSF1↓, cFos↓, cJun↓, AP-1↓, Mcl-1↓, NF-kB↓, IRE1↑, ER Stress↑, ATF4↑, GRP78/BiP↑, MMP2↓, MMP9↓, TCF-4↓, MMP7↓, RadioS↑, TOP1↓, TOP2↓,
2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, ROS↑, Apoptosis↑, Bcl-2↓, BAX↑, cl‑Casp9↑, cl‑Casp3↑, Cyt‑c↑, lipid-P↓, TumCG↓, TumCA↓, TumCMig↓, TumCI↓, uPA↓, ERK↓, MMP9↓, NF-kB↓, cFos↓, cJun↓, AP-1↓, TumCCA↑, AR↓, mTORC1↓, mTORC2↓, TSC2↑, EGF↓, TGF-β↓, EMT↓, P-gp↓, PI3K↓, Akt↓, mTOR↓, eff↑, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, ChemoSen↑, CDK2↓, CDK4↓, cycE/CCNE↓, cycD1/CCND1↓, P21↑, COX2↓, Wnt↓, EGFR↓, β-catenin/ZEB1↓, TCF-4↓, MMP7↓, RadioS↑, eff↑,
2844- FIS,    Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells
- in-vitro, OS, U2OS
tumCV↓, Apoptosis↑, Casp3↑, Casp8↑, Casp9↑, BAX↑, BAD↑, Bcl-2↓, Bcl-xL↓, PI3K↓, Akt↓, ERK↓, p‑JNK↑, p‑cJun↑, p‑p38↑, ROS↑, MMP↓, mTORC1↓, PTEN↑, p‑GSK‐3β↓, GSK‐3β↑, NF-kB↓, IKKα↑, Cyt‑c↑,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSTs↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↓, 1,   NRF2↑, 1,   ROS↓, 3,   ROS↑, 8,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   CDC2↓, 2,   CDC25↓, 3,   EGF↓, 2,   MEK↓, 1,   MMP↓, 7,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 3,   AMPK↑, 3,   cMyc↓, 1,   PCK1↓, 1,  

Cell Death ⓘ

Akt↓, 6,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAD↑, 4,   Bak↑, 1,   BAX↑, 7,   Bcl-2↓, 9,   Bcl-xL↓, 2,   BID↑, 1,   BIM↑, 4,   Casp↑, 2,   Casp3↑, 7,   cl‑Casp3↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 2,   Chk2↑, 1,   Cyt‑c↑, 7,   Diablo↑, 4,   DR4↑, 1,   DR5↑, 3,   Fas↑, 2,   IAP2↓, 1,   p‑JNK↑, 1,   MAPK↓, 3,   Mcl-1↓, 4,   Myc↓, 1,   p27↑, 1,   p38↓, 1,   p‑p38↓, 1,   p‑p38↑, 1,   survivin↓, 1,   TRAIL↑, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 4,   p‑cJun↑, 1,   p‑H3↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   ER Stress↑, 2,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 2,   IRE1↑, 2,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3s↑, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   CHK1↑, 1,   DNAdam↑, 4,   P53↑, 3,   cl‑PARP↑, 5,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 6,   CDK4↓, 6,   cycA1/CCNA1↓, 2,   cycD1/CCND1↓, 6,   cycE/CCNE↓, 2,   P21↑, 4,   Securin↓, 1,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 4,   EMT↓, 3,   ERK↓, 2,   p‑ERK↓, 1,   GSK‐3β↑, 2,   p‑GSK‐3β↓, 1,   mTOR↓, 5,   p‑mTOR↓, 1,   mTORC1↓, 4,   mTORC2↓, 3,   PI3K↓, 4,   PTEN↑, 1,   RAS↓, 1,   STAT3↓, 1,   TCF↑, 1,   TCF-4↓, 2,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 5,  

Migration ⓘ

AP-1↓, 2,   Ca+2↑, 2,   E-cadherin↓, 1,   E-cadherin↑, 3,   Fibronectin↓, 2,   Ki-67↓, 1,   MET↓, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 4,   MMP3↓, 1,   MMP7↓, 4,   MMP9↓, 4,   MMPs↓, 1,   N-cadherin↓, 2,   Rho↓, 1,   Snail↓, 2,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 2,   Twist↓, 2,   uPA↓, 6,   Vim↓, 3,   Zeb1↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↓, 1,   ATF4↑, 2,   EGFR↓, 4,   eNOS↓, 1,   VEGF↓, 2,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   IKKα↑, 1,   JAK1↓, 1,   NF-kB↓, 7,   NF-kB↑, 1,   p65↓, 1,   PGE2↓, 2,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   Dose↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 6,   Half-Life↓, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 4,   HER2/EBBR2↓, 1,   Ki-67↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   RenoP↑, 2,  
Total Targets: 167

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   NRF2↑, 1,  

DNA Damage & Repair ⓘ

p16↓, 1,   P53↓, 1,  

Cell Cycle & Senescence ⓘ

P21↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,  

Functional Outcomes ⓘ

neuroP↑, 2,  
Total Targets: 7

Scientific Paper Hit Count for: Bcl-2, B-cell CLL/lymphoma 2
9 Fisetin
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#:78  Target#:27  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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