Quercetin / SIRT1 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


SIRT1, Sirtuin 1 protein: Click to Expand ⟱
Source:
Type:
SIRT1 (Sirtuin 1) is a protein that plays a crucial role in various cellular processes, including metabolism, stress resistance, and longevity. In the context of cancer, SIRT1 has been found to have both tumor-suppressing and tumor-promoting functions, depending on the type of cancer and the cellular context.
Expression Promotes: Breast, Prostate, Colorectal Cancer.
Expression Suppresses: Leukemia, Liver Cancers.
-aging process is associated with the inactivation of the silent information regulator T1 (SIRT1) protein.


Scientific Papers found: Click to Expand⟱
2339- QC,    Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation
- in-vivo, Nor, NA
*Inflam↓, *antiOx↑, *NLRP3↓, *Sepsis↓, *PKM2↓, *SIRT1↓,
2338- QC,    Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury
- Review, Nor, NA
*SIRT1↑, *NLRP3↓, *Inflam↓, *TNF-α↓, *IL1β↓, *IL6↓, *PKM2↓, *HO-1↑, *ROS↓, *NO↓, *MDA↓, *antiOx↑, *COX2↓, *HMGB1↓, *iNOS↓, *NF-kB↓,
3607- QC,    Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More
- Review, AD, NA - Review, Park, NA
*neuroP↑, *NRF2↑, *PONs↑, *antiOx↑, *Inflam↓, *SIRT1↑, *eff↑, *ROS↓, *cognitive↑, *eff↑, *lipid-P↓, *GSH↑, *GPx↑, *SOD↑, *NRF2↑,
3534- QC,  Lyco,    Synergistic protection of quercetin and lycopene against oxidative stress via SIRT1-Nox4-ROS axis in HUVEC cells
- in-vitro, Nor, HUVECs
*ROS↓, *NOX4↓, *Inflam↓, *NF-kB↓, *p65↓, *SIRT1↑, *cardioP↑, *IL6↓, *COX2↓,
5025- QC,    New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation
- Review, Nor, NA
*antiOx↑, *Inflam↓, *NRF2↓, *ROS↓, *cardioP↑, *HO-1↑, *Catalase↑, *GPx↑, *NQO1↑, *SIRT1↑,
3350- QC,    Quercetin and the mitochondria: A mechanistic view
- Review, NA, NA
*antiOx↑, *Inflam↓, *NRF2↑, ROS⇅, *NRF2↑, *HO-1↑, *PPARα↑, *PGC-1α↑, *SIRT1↑, *ATP↑, ATP↓, ERK↓, cl‑PARP↑, Casp9↑, Casp8↑, BAX↑, MMP↓, Cyt‑c↑, Casp3↑, HSP27↓, HSP72↓, RAS↓, Raf↓,
3365- QC,    Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways
- in-vivo, Sepsis, NA
*ER Stress↓, *PDI↓, *CHOP↓, *GRP78/BiP↓, *ATF6↓, *PERK↓, *IRE1↓, *MMP↑, *SOD↑, *ROS↓, *MDA↓, *SIRT1↑, *AMPK↑, *Sepsis↓,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ROS⇅, 1,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 1,   Raf↓, 1,  

Cell Death

BAX↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,  

Protein Folding & ER Stress

HSP27↓, 1,   HSP72↓, 1,  

DNA Damage & Repair

cl‑PARP↑, 1,  

Proliferation, Differentiation & Cell State

ERK↓, 1,   RAS↓, 1,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 5,   Catalase↑, 1,   GPx↑, 2,   GSH↑, 1,   HO-1↑, 3,   lipid-P↓, 1,   MDA↓, 2,   NOX4↓, 1,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 4,   ROS↓, 5,   SOD↑, 2,  

Mitochondria & Bioenergetics

ATP↑, 1,   MMP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 1,   PKM2↓, 2,   PONs↑, 1,   PPARα↑, 1,   SIRT1↓, 1,   SIRT1↑, 6,  

Cell Death

iNOS↓, 1,  

Protein Folding & ER Stress

ATF6↓, 1,   CHOP↓, 1,   ER Stress↓, 1,   GRP78/BiP↓, 1,   IRE1↓, 1,   PERK↓, 1,  

Angiogenesis & Vasculature

NO↓, 1,   PDI↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   HMGB1↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 6,   NF-kB↓, 2,   p65↓, 1,   TNF-α↓, 1,  

Protein Aggregation

NLRP3↓, 2,  

Drug Metabolism & Resistance

eff↑, 2,  

Clinical Biomarkers

IL6↓, 2,  

Functional Outcomes

cardioP↑, 2,   cognitive↑, 1,   neuroP↑, 1,  

Infection & Microbiome

Sepsis↓, 2,  
Total Targets: 46

Scientific Paper Hit Count for: SIRT1, Sirtuin 1 protein
7 Quercetin
1 Lycopene
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#:634  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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