Quercetin / cFLIP Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


cFLIP, cellular FLICE-like inhibitory protein: Click to Expand ⟱
Source:
Type: protein
c-FLIP (cellular FLICE-like inhibitory protein) also know as FLIP
- is a protein that plays a crucial role in the regulation of apoptosis, or programmed cell death.
It is a key regulator of the extrinsic pathway of apoptosis, which is mediated by death receptors such as Fas and TNF-R1.
c-FLIP is a pseudokinase that can inhibit the activation of caspase-8, a key enzyme in the extrinsic pathway of apoptosis. By inhibiting caspase-8 activation, c-FLIP can prevent the initiation of the apoptotic cascade and promote cell survival.
In cancer, c-FLIP is often overexpressed, which can contribute to the development and progression of the disease.
Scientific Papers found: Click to Expand⟱
910- QC,    The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism
tumCV↓, Apoptosis↑, PI3k/Akt/mTOR↓, Wnt/(β-catenin)↓, MAPK↝, ERK↝, TumCCA↑, H2O2↑, ROS↑, TumAuto↑, MMPs↓, P53↑, Casp3↑, Hif1a↓, cFLIP↓, IL6↓, IL10↓, lactateProd↓, Glycolysis↓, PKM2↓, GLUT1↓, COX2↓, VEGF↓, OCR↓, ECAR↓, STAT3↓, MMP2↓, MMP9:TIMP1↓, mTOR↓,
916- QC,    Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells
- Review, Ovarian, NA
COX2↓, CRP↓, ER Stress↑, Apoptosis↑, GRP78/BiP↑, CHOP↑, p‑STAT3↓, PI3K↓, Akt↓, mTOR↓, cMyc↓, cycD1/CCND1↓, cFLIP↓, IL6↓, IL10↓,
914- QC,    Quercetin and Cancer Chemoprevention
- Review, NA, NA
GSH↓, ROS↑, TumCCA↑, Ca+2↑, MMP↓, Casp3↑, Casp8↑, Casp9↑, β-catenin/ZEB1↓, AMPKα↑, ASK1↑, p38↑, TRAIL↑, DR5↑, cFLIP↓, Apoptosis↑,
3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*ROS↓, *IronCh↓, *lipid-P↓, *GSH↑, *NRF2↑, TumCCA↑, ER Stress↑, P53↑, CDK2↓, cycA1/CCNA1↓, CycB/CCNB1↓, cycE/CCNE↓, cycD1/CCND1↓, PCNA↓, P21↑, p27↑, PI3K↓, Akt↓, mTOR↓, STAT3↓, cFLIP↓, cMyc↓, survivin↓, DR5↓, *Inflam↓, *IL6↓, *IL8↓, COX2↓, 5LO↓, *cardioP↑, *FASN↓, *AntiAg↑, *MDA↓,
3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*Inflam↓, *antiOx↑, *AntiCan↑, Casp3↓, p‑Akt↓, p‑mTOR↓, p‑ERK↓, β-catenin/ZEB1↓, Hif1a↓, AntiAg↓, VEGFR2↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2↓, cFLIP↓, cycD1/CCND1↓, cMyc↓, IL6↓, IL10↓, Cyt‑c↑, TumCCA↑, DNMTs↓, HDAC↓, ac‑H3↑, ac‑H4↑, Diablo↑, Casp3↑, Casp9↑, PARP1↑, eff↑, PTEN↑, VEGF↓, NO↓, iNOS↓, ChemoSen↑, eff↑, eff↑, eff↑, uPA↓, CXCR4↓, CXCL12↓, CLDN2↓, CDK6↓, MMP9↓, TSP-1↑, Ki-67↓, PCNA↓, ROS↑, ER Stress↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   H2O2↑, 1,   ROS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   ECAR↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 3,   ASK1↑, 1,   BAX↑, 1,   Casp3↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 2,   cFLIP↓, 5,   Cyt‑c↑, 1,   Diablo↑, 1,   DR5↓, 1,   DR5↑, 1,   iNOS↓, 1,   MAPK↝, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 1,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 3,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNMTs↓, 1,   P53↑, 3,   PARP1↑, 1,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↝, 1,   p‑ERK↓, 1,   HDAC↓, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   PI3K↓, 3,   PTEN↑, 1,   STAT3↓, 3,   p‑STAT3↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↓, 1,   Ca+2↑, 1,   CLDN2↓, 1,   CXCL12↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP9↓, 1,   MMP9:TIMP1↓, 1,   MMPs↓, 2,   N-cadherin↓, 1,   PKCδ↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumMeta↓, 1,   uPA↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 2,   NO↓, 1,   VEGF↓, 2,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 1,   CXCR4↓, 1,   IL10↓, 3,   IL6↓, 3,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 4,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   IL6↓, 3,   Ki-67↓, 1,  
Total Targets: 100

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Metal & Cofactor Biology ⓘ

IronCh↓, 1,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 1,  

Migration ⓘ

AntiAg↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL6↓, 1,   IL8↓, 1,   Inflam↓, 2,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,  
Total Targets: 15

Scientific Paper Hit Count for: cFLIP, cellular FLICE-like inhibitory protein
5 Quercetin
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#:140  Target#:885  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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