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


UPR, Unfolded Protein Response: Click to Expand ⟱
Source:
Type:
Cellular stress response related to the endoplasmic reticulum (ER) stress, which involves protein folding, quality control, and signaling pathways. The unfolded protein response (UPR) is the cells' way of maintaining the balance of protein folding in the endoplasmic reticulum. (UPR) is triggered by the presence of misfolded proteins in the endoplasmic reticulum.
The UPR is a cellular stress response activated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER).
- It is primarily mediated by three ER-resident sensors: IRE1α, PERK, and ATF6.

Cancer cells often experience high levels of protein synthesis, hypoxia, nutrient deprivation, and oxidative stress, all of which can activate the UPR.
– Numerous studies have reported that key UPR components (e.g., GRP78/BiP, IRE1α, PERK, CHOP) are overexpressed in various malignancies such as breast, pancreatic, lung, and prostate cancers.

Unfolded Protein Response is typically upregulated in cancers and is associated with poorer prognosis due to its role in promoting cell survival, adaptation to stress, and therapeutic resistance. Although the UPR harbors the potential for tumor-suppressive (apoptotic) effects under severe stress conditions, its predominant activation in tumors supports an adaptive, protumorigenic state that facilitates cancer progression. Targeting UPR components and modulating this balance remain promising therapeutic strategies.
Scientific Papers found: Click to Expand⟱
3337- QC,    Endoplasmic Reticulum Stress-Relieving Effect of Quercetin in Thapsigargin-Treated Hepatocytes
- in-vitro, NA, HepG2
*Inflam↓, quercetin exerts anti-inflammatory and anti–insulin resistance actions by suppressing UPR in cells experiencing ER stress
*UPR↓,
*GRP58↓, (GRP78) and the downstream proteins such as X-box binding protein 1 (XBP1). The increased expression was significantly inhibited by quercetin, indicating that this compound can relieve ER stress
*XBP-1↓,
*ER Stress↓, previous reports as well as our results, we suggest that quercetin can inhibit ER stress in hepatocytes
*antiOx↑, Quercetin, a well-known antioxidant, is one of the most abundant flavonols in vegetables and fruits and has been shown to have many pharmacological actions
TNF-α↓, Quercetin suppressed the increased expression of TNF-α significantly and dose-dependently
p‑eIF2α↓, quercetin treatment suppressed the phosphorylation of eIF2α, IRE1α and JNK and the mRNA expression of XBP-1, GRP78 and CHOP
p‑IRE1↓,
p‑JNK↓,
CHOP↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Results for Effect on Cancer/Diseased Cells:
CHOP↓,1,   p‑eIF2α↓,1,   p‑IRE1↓,1,   p‑JNK↓,1,   TNF-α↓,1,  
Total Targets: 5

Results for Effect on Normal Cells:
antiOx↑,1,   ER Stress↓,1,   GRP58↓,1,   Inflam↓,1,   UPR↓,1,   XBP-1↓,1,  
Total Targets: 6

Scientific Paper Hit Count for: UPR, Unfolded Protein Response
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:459  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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