Quercetin / PI3K/Akt 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.
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

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


PI3K/Akt, PI3K/Akt signaling: Click to Expand ⟱
Source: HalifaxProj(inhibit) TCGA
Type:
The PI3K/Akt signaling pathway plays a crucial role in various cellular processes, including growth, proliferation, survival, and metabolism.
Pathway Components:
Phosphoinositide 3-kinases (PI3Ks): A family of enzymes that phosphorylate the inositol ring of phosphatidylinositol, leading to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3).
Akt (Protein Kinase B): A serine/threonine kinase that is activated by PIP3. Once activated, Akt phosphorylates various substrates involved in cell survival and growth.
Overactivation can lead to uncontrolled cell growth.
Angiogenesis: Akt can promote the expression of pro-angiogenic factors, facilitating the formation of new blood vessels to supply tumors with nutrients and oxygen.
Scientific Papers found: Click to Expand⟱
99- QC,    Quercetin Inhibits Epithelial-to-Mesenchymal Transition (EMT) Process and Promotes Apoptosis in Prostate Cancer via Downregulating lncRNA MALAT1
- in-vitro, Pca, PC3
EMT↓, E-cadherin↑, N-cadherin↓, Ki-67↓, PI3K/Akt↓, MALAT1↓, TumCG↓,
52- QC,    Effect of Quercetin on Cell Cycle and Cyclin Expression in Ovarian Carcinoma and Osteosarcoma Cell Lines
- in-vitro, BC, MCF7 - in-vitro, Ovarian, SKOV3 - in-vitro, OS, U2OS
Bcl-2↓, BAX↑, PI3K/Akt↓, cycD1/CCND1↓, TumCCA↑,
54- QC,    Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways
- in-vitro, BC, MCF7
EMT↓, E-cadherin↑, Vim↓, MMP2↓, NOTCH1↓, PI3K/Akt↓, PI3k/Akt/mTOR↓, p‑Akt↓, EZH2↓, H3K27ac↓, TumCCA↑, CSCs↓, CDK1↓, CycB/CCNB1↓, Bcl-xL↓, Bcl-2↓, Nanog↓, H3↓,
55- QC,    Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling
- in-vitro, GC, GCSCs
Bcl-2↓, BAX↑, Cyt‑c↑, MMP↓, PI3K/Akt↓, Casp3↑, Casp9↑, TumCG↓, Apoptosis↑, CSCs↓,
38- QC,    Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, GSH↓, PI3K/Akt⇅,
39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, NA
ROS↑, GSH↓, IL6↓, COX2/PTGS2↓, IL8↓, iNOS↓, TNF-α↓, MAPK↑, ERK↑, SOD↑, ATP↓, Casp↑, PI3K/Akt↓, mTOR↓, NOTCH1↓, Bcl-2↓, BAX↑, IFN-γ↓, TumCP↓, TumCCA↑, Akt↓, P70S6K↓, *Keap1↓, *GPx↑, *Catalase↑, *HO-1↑, *NRF2↑, NRF2↑, eff↑, HIF-1↓,
96- QC,  docx,    Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways
- vitro+vivo, Pca, LNCaP - in-vitro, Pca, PC3
PI3K/Akt↓, Ki-67↓, BAX↑, Bcl-2↓, EpCAM↓, Twist↓, E-cadherin↑, P-gp/ABCB1↓, TumCP↓, TumCMig↓, TumCI↓,
89- QC,  doxoR,    Quercetin reverses the doxorubicin resistance of prostate cancer cells by downregulating the expression of c-met
- in-vitro, Pca, PC3
PI3K/Akt↓, cMET↓, Casp3↑, Casp9↑, MMP↓, ChemoSen↑, ROS↑,
71- QC,    Role of Bax in quercetin-induced apoptosis in human prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PrEC - in-vitro, Pca, YPEN-1 - in-vitro, Pca, HCT116
Casp8↑, Casp9↑, PARP↑, BAD↓, BAX↑, PI3K/Akt↓, Cyt‑c↑, selectivity↑,
82- QC,  ATG,    Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓, PI3K/Akt↓, miR-21↓, STAT3↓, BAD↓, PRAS40↓, GSK‐3β↓, PSA↓, NKX3.1↑, Bax:Bcl2↑, miR-19b↓, miR-148a↓, AMPKα↓, TumCP↓, chemoPv↑, TumCMig↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↓, 2,   NRF2↑, 1,   ROS↑, 2,   ROS⇅, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

PI3K/Akt↓, 9,   PI3K/Akt⇅, 1,   PI3k/Akt/mTOR↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 1,   BAD↓, 2,   BAX↑, 5,   Bax:Bcl2↑, 1,   Bcl-2↓, 5,   Bcl-xL↓, 1,   Casp↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 3,   Cyt‑c↑, 2,   iNOS↓, 1,   MAPK↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

AMPKα↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

EZH2↓, 1,   H3↓, 1,   miR-21↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

NKX3.1↑, 1,   PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

cMET↓, 1,   CSCs↓, 2,   EMT↓, 2,   EpCAM↓, 1,   ERK↑, 1,   GSK‐3β↓, 1,   H3K27ac↓, 1,   mTOR↓, 1,   Nanog↓, 1,   NOTCH1↓, 2,   P70S6K↓, 1,   STAT3↓, 1,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

E-cadherin↑, 3,   Ki-67↓, 2,   MALAT1↓, 1,   miR-148a↓, 1,   miR-19b↓, 1,   MMP2↓, 1,   N-cadherin↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 3,   Twist↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

HIF-1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IFN-γ↓, 1,   IL6↓, 1,   IL8↓, 1,   PSA↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↑, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 1,   EZH2↓, 1,   IL6↓, 1,   Ki-67↓, 2,   PSA↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,   PRAS40↓, 1,  
Total Targets: 79

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   GPx↑, 1,   HO-1↑, 1,   Keap1↓, 1,   NRF2↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: PI3K/Akt, PI3K/Akt signaling
10 Quercetin
1 Docetaxel
1 doxorubicin
1 Arctigenin
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#:253  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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