Quercetin / GRP78/BiP 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


GRP78/BiP, HSPA5: Click to Expand ⟱
Source:
Type:
GRP78 (Pgp, BiP or ERp72) is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors.
-GRP78 protein, a marker for endoplasmic reticulum stress
-GRP78’s role as a master regulator of the unfolded protein response (UPR) and cellular stress responses
The association of P-gp and inhibition of cell death in cancerous cells has also been reported in several studies including in hepatocellular, colorectal, prostate cancer, and gastric cancer. Although counterintuitive due to its prominent role in cancer resistance, P-gp has been linked to favorable prognosis.
ERp72 can promote cancer cell proliferation, migration, and invasion by regulating various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways. Additionally, ERp72 can also inhibit apoptosis (programmed cell death) in cancer cells, which can contribute to tumor progression. Overexpressed in: Breast, lung colorectal, prostrate, ovarian, pancreatic.

-GRP78 is frequently upregulated in a variety of solid tumors and hematological malignancies.
-Overexpression of GRP78 in cancer cells is often regarded as a marker of increased ER stress due to the reduced oxygen and nutrient supply typically encountered in the tumor microenvironment.
-Elevated GRP78 levels can contribute to tumor cell survival by enhancing the adaptive UPR, allowing cancer cells to cope with therapeutic and metabolic stress.
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↓,
66- QC,    Emerging impact of quercetin in the treatment of prostate cancer
- Review, Pca, NA
CycB/CCNB1↓, CDK1↓, EMT↓, PI3K↓, MAPK↓, Wnt/(β-catenin)↓, PSA↓, VEGF↓, PARP↑, Casp3↑, Casp9↑, DR5↑, ROS⇅, Shh↓, P53↑, P21↑, EGFR↓, TumCCA↑, ROS↑, miR-21↓, TumCP↓, selectivity↑, PDGF↓, EGF↓, TNF-α↓, VEGFR2↓, mTOR↓, cMyc↓, MMPs↓, GRP78/BiP↑, CHOP↑,
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↓,
3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, α-SMA↑, TumCP↓, tumCV↓, TumVol↓, TumCI↓, TumMeta↓, TumCMig↓, ROS↑, Apoptosis↑, BioAv↓, *neuroP↑, *antiOx↑, *Inflam↓, *Aβ↓, *cardioP↑, MMP↓, Cyt‑c↑, MMP2↓, MMP9↓, EMT↓, MMPs↓, Twist↓, Slug↓, Ca+2↑, AIF↑, Endon↑, P-gp↓, LDH↑, HK2↓, PKA↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, GRP78/BiP↑, Casp12↑, CHOP↑,
3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, TumCCA↑, p‑pRB↓, CDK2↑, CycB/CCNB1↓, CDK1↓, EMT↓, PI3K↓, MAPK↓, Wnt↓, ROS↑, miR-21↑, Akt↓, NF-kB↓, FasL↑, Bak↑, BAX↑, Bcl-2↓, Casp3↓, Casp9↑, P53↑, p38↑, MAPK↑, Cyt‑c↑, PARP↓, CHOP↑, ROS↓, LDH↑, GRP78/BiP↑, ERK↑, MDA↓, SOD↑, GSH↑, NRF2↑, VEGF↓, PDGF↓, EGF↓, FGF↓, TNF-α↓, TGF-β↓, VEGFR2↓, EGFR↓, FGFR1↓, mTOR↓, cMyc↓, MMPs↓, LC3B-II↑, Beclin-1↑, IL1β↓, CRP↓, IL10↓, COX2↓, IL6↓, TLR4↓, Shh↓, HER2/EBBR2↓, NOTCH↓, DR5↑, HSP70/HSPA5↓, CSCs↓, angioG↓, MMP2↓, MMP9↓, IGFBP3↑, uPA↓, uPAR↓, RAS↓, Raf↓, TSP-1↑,
3366- QC,    Quercetin Attenuates Endoplasmic Reticulum Stress and Apoptosis in TNBS-Induced Colitis by Inhibiting the Glucose Regulatory Protein 78 Activation
- in-vivo, IBD, NA
*Apoptosis↓, *Inflam↓, *ROS↓, *ER Stress↓, *TNF-α↓, *MPO↓, *p‑JNK↓, *Casp12↓, *GRP78/BiP↓, *antiOx↑, *NF-kB↓,
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↓,
3364- QC,    Quercetin Protects Human Thyroid Cells against Cadmium Toxicity
- in-vitro, Nor, NA
*MDA↓, *GRP78/BiP↓,
3363- QC,    The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation
- in-vitro, Nor, HBMECs
*Apoptosis↓, *angioG↑, *NRF2↑, *Keap1↓, *ATF6↓, *GRP78/BiP↓, *CLDN5↑, *ZO-1↑, *MMP↑, *BBB↑, *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↑,
3361- QC,    Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats
- in-vivo, Nor, NA - in-vitro, NA, NA
*BG↓, *ROS↓, *SOD↑, *MDA↓, *ER Stress↓, *iNOS↓, *CHOP↓, *GRP78/BiP↓, *antiOx↓, *Inflam↓, *JAK2↑, *STAT3?,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 4,   ROS⇅, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   EGF↓, 2,   FGFR1↓, 1,   MMP↓, 2,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDH↑, 2,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 4,   Bak↑, 1,   BAX↑, 2,   Bcl-2↓, 2,   Casp12↑, 1,   Casp3↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 3,   cFLIP↓, 1,   Cyt‑c↑, 2,   DR5↑, 2,   Endon↑, 1,   FasL↑, 1,   MAPK↓, 2,   MAPK↑, 1,   p38↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   miR-21↑, 1,   p‑pRB↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

c-ATF6↑, 1,   ATFs↑, 1,   CHOP↑, 7,   ER Stress↑, 4,   GRP78/BiP↑, 7,   HSP70/HSPA5↓, 1,   IRE1↑, 1,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   PARP↓, 1,   PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 1,   CDK2↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 3,   ERK↑, 1,   FGF↓, 1,   IGFBP3↑, 1,   mTOR↓, 3,   NOTCH↓, 1,   PI3K↓, 3,   RAS↓, 1,   Shh↓, 2,   p‑STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

Ca+2↑, 2,   FAK↓, 1,   MMP2↓, 2,   MMP9↓, 2,   MMPs↓, 3,   PDGF↓, 2,   PKA↓, 1,   Slug↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 3,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 1,   uPAR↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 2,   VEGF↓, 2,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 2,   IL10↓, 2,   IL1β↓, 1,   IL6↓, 2,   NF-kB↓, 1,   PSA↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

CRP↓, 2,   EGFR↓, 2,   HER2/EBBR2↓, 1,   IL6↓, 2,   LDH↑, 2,   PSA↓, 1,  

Functional Outcomes ⓘ

TumVol↓, 1,  
Total Targets: 119

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 2,   Keap1↓, 1,   MDA↓, 3,   MPO↓, 1,   NRF2↑, 1,   ROS↓, 4,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Apoptosis↓, 2,   Casp12↓, 1,   iNOS↓, 1,   p‑JNK↓, 1,  

Protein Folding & ER Stress ⓘ

ATF6↓, 2,   CHOP↓, 2,   ER Stress↓, 4,   GRP78/BiP↓, 5,   IRE1↓, 1,   PERK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

STAT3?, 1,  

Migration ⓘ

ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   CLDN5↑, 1,   PDI↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 3,   JAK2↑, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Clinical Biomarkers ⓘ

BG↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 36

Scientific Paper Hit Count for: GRP78/BiP, HSPA5
12 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#:356  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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