condition found tbRes List
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


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↑, Quercetin can result in stimulate the ER stress pathway that lead to the cause of cell death and apoptosis
Apoptosis↑,
GRP78/BiP↑,
CHOP↑,
p‑STAT3↓, quercetin suppresses STAT3 and PI3K/AKT/mTOR pathways
PI3K↓,
Akt↓,
mTOR↓,
cMyc↓, leading to downregulate the prosurvival cellular proteins expression, including cMyc, cyclin D1, and c-FLIP
cycD1↓,
cFLIP↓,
IL6↓, decreased the IL-6 and IL-10 release
IL10↓,

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↓, Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose, and inhibited oxidative stress.
*ROS↓,
*SOD↑, Both doses of quercetin reduced reactive oxygen species and malondialdehyde levels, and increased superoxide dismutase level in HG-treated cells.
*MDA↓,
*ER Stress↓, quercetin inhibits endoplasmic reticulum stress
*iNOS↓, Quercetin could eliminate the upregulation of iNOS, ET-1, and AR mRNA levels in HG-treated cells
*CHOP↓, HG treatment increased CHOP and Grp78 mRNA and protein levels in HG-treated cells, and two doses (5 or 10 μM) of quercetin all decreased these levels
*GRP78/BiP↓,
*antiOx↓, Quercetin is a natural polyphenol compound with anti-inflammatory [37], anti-oxidant [38], and blood sugar lowering properties
*Inflam↓,
*JAK2↑, Our results in vitro showed that quercetin treatment upregulated the phosphorylation levels of JAK2 and STAT3 in HG treated cells. (activating of the JAK2/STAT3 pathway could inhibit ER stress)
*STAT3?,

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↑, The apoptosis rate in the quercetin group increased significantly in comparison with the blank control group,
cycD1↓, Cyclin D1 showed a tendency to decrease progressively
Casp3↑, Caspase-3, GRP78, and CHOP expression levels in the quercetin intervention group rose significantly in comparison with the blank control group
GRP78/BiP↑,
CHOP↑,
tumCV↓, viability of the cervical cancer HeLe cells was inhibited by quercetin in a dose-dependent manner
IRE1↑, The IRE1, p-Perk, and c-ATF6 levels in the quercetin intervention group (20, 40, and 80 μmol/L) rose gradually in comparison with the blank control group
p‑PERK↑,
c-ATF6↑,
ER Stress↑, quercetin can induce ERS to initiate HeLe cell apoptosis.

3363- QC,    The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation
- in-vitro, Nor, HBMECs
*Apoptosis↓, Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis.
*angioG↑,
*NRF2↑, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression.
*Keap1↓,
*ATF6↓,
*GRP78/BiP↓,
*CLDN5↑, quercetin could increase the expression of Claudin-5 and Zonula occludens-1.
*ZO-1↑,
*MMP↑, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis.
*BBB↑, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
*ROS↓, Quercetin Could Inhibit Oxidative Stress
*ER Stress↓, In our study, ER stress was activated by H/R, and the levels of ATF6 and GRP78 were increased. Quercetin at 1 μmol/L was able to significantly reduce the protein levels of both, inhibit ER stress, and protect HBMECs from H/R injury

3364- QC,    Quercetin Protects Human Thyroid Cells against Cadmium Toxicity
- in-vitro, Nor, NA
*MDA↓, MDA production was increased significantly after incubation with CdCl 2 1 and 10 μM compared with untreated cells (p < 0.001). This effect was significantly attenuated when the cultures were supple‐ mented with quercetin
*GRP78/BiP↓, A significant increase in GRP78 protein expression was detected in Nthy‐ori‐3‐1 cells exposed to 0.1 or 1 μM of CdCl 2 for 2 h compared with untreated cells. Again, this action was reversed by pretreatment with quercetin 5 μM

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↓, quercetin could inhibit the level of ER stress as evidenced by decreased mRNA expression of PDI, CHOP, GRP78, ATF6, PERK, IRE1α
*PDI↓,
*CHOP↓,
*GRP78/BiP↓,
*ATF6↓,
*PERK↓,
*IRE1↓,
*MMP↑, and improve mitochondrial function, as presented by increased MMP, SOD level and reduced production of ROS, MDA.
*SOD↑,
*ROS↓,
*MDA↓,
*SIRT1↑, quercetin upregulated SIRT1/AMPK mRNA expression.
*AMPK↑,
*Sepsis↓, quercetin could protect against sepsis-induced ALI by suppressing oxidative stress-mediated ER stress and mitochondrial dysfunction via induction of the SIRT1/AMPK pathways.

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↓, quercetin improved TNBS-induced histopathological alterations, apoptosis, inflammation, oxidative stress, and ER stress
*Inflam↓,
*ROS↓,
*ER Stress↓, suggests that quercetin has a regulatory effect on ER stress-mediated apoptosis, and thus may be beneficial in treating IBD.
*TNF-α↓, Quercetin reduced the TNF-α and MPO levels associated with colitis
*MPO↓,
*p‑JNK↓, The HSCORE values of p-JNK (p < 0.001), caspase-12 (p < 0.001), and GRP78 (p = 0.004) were lowered in the quercetin group when compared to the colitis group
*Casp12↓,
*GRP78/BiP↓,
*antiOx↑, protective effect of quercetin in IBD, attributed to its antioxidant properties and NF-kB inhibition
*NF-kB↓,

3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
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↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

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↓, In oral cancer cells, quercetin could inhibit EMT via up-regulation of claudin-1 and E-cadherin and down-regulation of α-SMA, vimentin, fibronectin, and Slug [29]
α-SMA↑, OSC20 Invasion: ↓Migration, ↑Expression of epithelial markers (E-cadherin & claudin-1), ↑Expression of mesenchymal markers (fibronectin, vimentin, & α-SMA),
TumCP↓, quercetin significantly reduced cancer cell proliferation, cell viability, tumor volume, invasion, metastasis and migration
tumCV↓,
TumVol↓,
TumCI↓,
TumMeta↓,
TumCMig↓,
ROS↑, This anti-cancer agent induced oxidative stress and apoptosis in the cancer cells.
Apoptosis↑,
BioAv↓, The efficacy of quercetin (as lipophilic) is much impacted by its poor absorption rates, which define its bioavailability. The research on quercetin's bioavailability in animal models shows it may be as low as 10%
*neuroP↑, quercetin has been observed to exhibit neuroprotective effects in Alzheimer's disease through its anti-oxidants, and anti-inflammatory properties and inhibition of amyloid-β (Aβ) fibril formation
*antiOx↑,
*Inflam↓,
*Aβ↓,
*cardioP↑, Additionally, quercetin protects the heart by stopping oxidative stress, inflammation, apoptosis, and protein kinases
MMP↓, ↓MMP, ↑Cytosolic Cyt. C,
Cyt‑c↑,
MMP2↓, ↓Activation MMP-2 & MMP-9, ↓Expression levels of EMT inducers & MMPs, Downregulated Twist & Slug
MMP9↓,
EMT↓,
MMPs↓,
Twist↓,
Slug↓,
Ca+2↑, ↑Apoptosis, ↑ROS, ↑Ca2+ production, ↑Activities of caspase‑3, caspase‑8 & caspase‑9
AIF↑, ↑Mitochondrial release of Cyt. C, AIF, & Endo G
Endon↑,
P-gp↓, ↓ Protein levels of P-gp, & P-gp Expression
LDH↑, ↑LDH release
HK2↓, CAL27 cells) 80µM/24h Molecular markers: ↓Activities of HK, PK, & LDH, ↓Glycolysis, ↓Glucose uptake, ↓Lactate production, ↓Viability, ↓G3BP1, & YWHA2 protein levels
PKA↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
GRP78/BiP↑, Quercetin controls the activation of intracellular Ca2+ and calpain-1, which then activates GRP78, caspase-12, and C/EBP homologous protein (CHOP) in oral cancer cells
Casp12↑,
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↓,
cycD1↓, proteins
ATFs↑,
GRP78/BiP↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp8↑,
Casp9↑,
ER Stress↑, stress
CHOP↑,


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

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   Akt↓,2,   angioG↓,1,   Apoptosis↑,3,   c-ATF6↑,1,   ATFs↑,1,   Bak↑,1,   BAX↑,2,   Bcl-2↓,2,   Beclin-1↑,1,   BioAv↓,1,   Ca+2↑,1,   Casp12↑,1,   Casp3↓,1,   Casp3↑,2,   Casp8↑,1,   Casp9↑,2,   CDK1↓,1,   CDK2↓,1,   CDK2↑,1,   cFLIP↓,1,   CHOP↑,5,   cMyc↓,2,   COX2↓,2,   CRP↓,2,   CSCs↓,1,   CycB↓,1,   cycD1↓,3,   cycE↓,1,   Cyt‑c↑,2,   DR5↑,1,   EGF↓,1,   EGFR↓,1,   EMT↓,2,   Endon↑,1,   ER Stress↑,3,   ERK↑,1,   FAK↓,1,   FasL↑,1,   FGF↓,1,   FGFR1↓,1,   GlucoseCon↓,1,   Glycolysis↓,1,   GRP78/BiP↑,5,   GSH↑,1,   HER2/EBBR2↓,1,   HK2↓,1,   HSP70/HSPA5↓,1,   IGFBP3↑,1,   IL10↓,2,   IL1β↓,1,   IL6↓,2,   IRE1↑,1,   lactateProd↓,1,   LC3B-II↑,1,   LDH↑,2,   MAPK↓,1,   MAPK↑,1,   MDA↓,1,   miR-21↑,1,   MMP↓,1,   MMP2↓,2,   MMP9↓,2,   MMPs↓,2,   mTOR↓,2,   NF-kB↓,1,   NOTCH↓,1,   NRF2↑,1,   P-gp↓,1,   p38↑,1,   P53↑,1,   PARP↓,1,   PDGF↓,1,   p‑PERK↑,1,   PI3K↓,2,   PKA↓,1,   p‑pRB↓,1,   Raf↓,1,   RAS↓,1,   ROS↓,1,   ROS↑,2,   Shh↓,1,   Slug↓,1,   SOD↑,1,   p‑STAT3↓,1,   TGF-β↓,1,   TLR4↓,1,   TNF-α↓,1,   TSP-1↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   tumCV↓,2,   TumMeta↓,1,   TumVol↓,1,   Twist↓,1,   uPA↓,1,   uPAR↓,1,   VEGF↓,1,   VEGFR2↓,1,   Wnt↓,1,   α-SMA↓,1,   α-SMA↑,1,  
Total Targets: 104

Results for Effect on Normal Cells:
AMPK↑,1,   angioG↑,1,   antiOx↓,1,   antiOx↑,2,   Apoptosis↓,2,   ATF6↓,2,   Aβ↓,1,   BBB↑,1,   BG↓,1,   cardioP↑,1,   Casp12↓,1,   CHOP↓,2,   CLDN5↑,1,   ER Stress↓,4,   GRP78/BiP↓,5,   Inflam↓,3,   iNOS↓,1,   IRE1↓,1,   JAK2↑,1,   p‑JNK↓,1,   Keap1↓,1,   MDA↓,3,   MMP↑,2,   MPO↓,1,   neuroP↑,1,   NF-kB↓,1,   NRF2↑,1,   PDI↓,1,   PERK↓,1,   ROS↓,4,   Sepsis↓,1,   SIRT1↑,1,   SOD↑,2,   STAT3?,1,   TNF-α↓,1,   ZO-1↑,1,  
Total Targets: 36

Scientific Paper Hit Count for: GRP78/BiP, HSPA5
10 Quercetin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:356  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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