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| 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. EMIQ bioavialability is about 3X that of Quercetin (Example Natural Factors brand) Isoquercitrin is high bioaviability and efficiacy but at this time does not seem available as supplement. -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
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| The effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”. Possible Chemo-Sensitizers: -Curcumin -Resveratrol -EGCG -Quercetin -Genistein -Berberine -Piperine: alkaloid from black pepper -Ginsenosides: active components of ginseng -Silymarin -Allicin -Lycopene -Ellagic acid -Caffeic acid phenethyl ester -flavopiridol -oleandrin -Ursolic acid -butein -Betulinic acid |
| 26- | EGCG, | QC, | docx, | Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy |
| - | vitro+vivo, | Pca, | PC3 |
| 1493- | QC, | New quercetin-coated titanate nanotubes and their radiosensitization effect on human bladder cancer |
| - | NA, | Bladder, | NA |
| 2303- | QC, | doxoR, | Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1α in tumor and normal cells |
| - | in-vitro, | BC, | 4T1 | - | in-vivo, | NA, | NA |
| 53- | QC, | Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer |
| - | in-vitro, | BC, | MDA-MB-231 | - | NA, | NA, | MDA-MB-468 |
| 58- | QC, | doxoR, | Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin |
| - | in-vitro, | CRC, | HT-29 | - | in-vitro, | NA, | CD133+ |
| 63- | QC, | Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells |
| - | in-vitro, | Pca, | NA |
| 97- | QC, | HPT, | Effects of the flavonoid drug Quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo |
| - | in-vitro, | Pca, | PC3 |
| 89- | QC, | doxoR, | Quercetin reverses the doxorubicin resistance of prostate cancer cells by downregulating the expression of c-met |
| - | in-vitro, | Pca, | PC3 |
| 4787- | QC, | Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells |
| - | Review, | CRC, | NA |
| 4827- | QC, | CUR, | Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin |
| - | Review, | Var, | NA |
| 3353- | QC, | Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells |
| - | in-vitro, | Oral, | KON | - | in-vitro, | Nor, | MRC-5 |
| 3347- | QC, | Recent Advances in Potential Health Benefits of Quercetin |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 3368- | QC, | The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update |
| - | Review, | Var, | NA |
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
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