Quercetin / ER Stress 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


ER Stress, endoplasmic reticulum (ER) stress signaling pathway: Click to Expand ⟱
Source:
Type:
Protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress.
The endoplasmic reticulum (ER) stress signaling pathway plays a crucial role in maintaining cellular homeostasis and responding to various stressors, including those encountered in cancer. When cells experience stress, such as the accumulation of misfolded proteins, they activate a series of signaling pathways collectively known as the unfolded protein response (UPR). The UPR aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if the stress is unresolved, triggering apoptosis.
The activation of ER stress pathways can contribute to resistance against chemotherapy and targeted therapies. Cancer cells may utilize the UPR to survive treatment-induced stress, making it challenging to achieve effective therapeutic outcomes.

-ER stress-associated proteins include: phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12
Scientific Papers found: Click to Expand⟱
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↓,
91- QC,    The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells
- in-vitro, Pca, PC3
CDK2↓, cycE/CCNE↓, cycD1/CCND1↓, ATFs↑, GRP78/BiP↑, Bcl-2↓, BAX↑, Casp3↑, Casp8↑, Casp9↑, ER Stress↑, CHOP↑, TumCCA↑, DNAdam↑, AIF↑, Ca+2↑, MMP↓,
88- QC,  PacT,    Quercetin Enhanced Paclitaxel Therapeutic Effects Towards PC-3 Prostate Cancer Through ER Stress Induction and ROS Production
- vitro+vivo, Pca, PC3
ROS↑, ER Stress↑, TumCP↓, Apoptosis↑, TumCCA↑, TumCMig↓, GRP78/BiP↑, CHOP↑, TumCG↓,
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↑,
3362- QC,    The effect of quercetin on cervical cancer cells as determined by inducing tumor endoplasmic reticulum stress and apoptosis and its mechanism of action
- in-vitro, Cerv, HeLa
Apoptosis↑, cycD1/CCND1↓, Casp3↑, GRP78/BiP↑, CHOP↑, tumCV↓, IRE1↑, p‑PERK↑, c-ATF6↑, ER Stress↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 2,   cFLIP↓, 3,   Cyt‑c↑, 1,   Diablo↑, 1,   DR5↓, 1,   iNOS↓, 1,   p27↑, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

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

Protein Folding & ER Stress ⓘ

c-ATF6↑, 1,   ATFs↑, 1,   CHOP↑, 4,   ER Stress↑, 6,   GRP78/BiP↑, 4,   IRE1↑, 1,   p‑PERK↑, 1,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 2,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   p‑ERK↓, 1,   HDAC↓, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   PI3K↓, 3,   PTEN↑, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

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

Angiogenesis & Vasculature ⓘ

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

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CRP↓, 1,   CXCR4↓, 1,   IL10↓, 2,   IL6↓, 2,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 4,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   IL6↓, 2,   Ki-67↓, 1,  
Total Targets: 91

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: ER Stress, endoplasmic reticulum (ER) stress signaling pathway
6 Quercetin
1 Paclitaxel
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#:103  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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