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


JNK, c-Jun N-terminal kinase (JNK): Click to Expand ⟱
Source:
Type:
JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. Janus signaling promotes cancer cell survival.
JNK, or c-Jun N-terminal kinase, is a member of the mitogen-activated protein kinase (MAPK) family. It plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). JNK is activated in response to various stress signals, such as UV radiation, oxidative stress, and inflammatory cytokines.
JNK activation can promote apoptosis in cancer cells, acting as a tumor suppressor. However, in other contexts, it can promote cell survival and proliferation, contributing to tumor progression.

JNK is often unregulated in cancers, leading to increased cancer cell proliferation, survival, and resistance to apoptosis. This activation is typically associated with poor prognosis and aggressive tumor behavior.
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↓,

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↓,

3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
TumCCA↓, inhibition of the cell cycle;
HSPs↓, inhibition of heat shock proteins;
RAS↓, inhibition of Ras protein expression.
ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
Ca+2↑,
MMP↓,
Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
Endon↑,
MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
MMP2↓,
MMP7↓,
MMP-10↓,
VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
NF-kB↓,
p65↓,
iNOS↓,
COX2↓,
uPA↓,
PI3K↓,
FAK↓,
MEK↓,
ERK↓,
JNK↓,
p38↓,
cJun↓,
FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Ca+2↑,1,   CHOP↓,1,   cJun↓,1,   COX2↓,1,   Cyt‑c↑,1,   p‑eIF2α↓,1,   Endon↑,1,   ERK↓,1,   FAK↓,1,   FOXO3↑,1,   HSPs↓,1,   iNOS↓,1,   p‑IRE1↓,1,   JNK↓,1,   p‑JNK↓,1,   MEK↓,1,   MMP↓,1,   MMP-10↓,1,   MMP2↓,1,   MMP7↓,1,   MMP9↓,1,   NF-kB↓,1,   p38↓,1,   p65↓,1,   PI3K↓,1,   RAS↓,1,   ROCK1↑,1,   ROS↑,1,   TNF-α↓,1,   TumCCA↓,1,   uPA↓,1,   VEGF↓,1,  
Total Targets: 32

Results for Effect on Normal Cells:
antiOx↑,2,   Apoptosis↓,1,   Casp12↓,1,   ER Stress↓,2,   GRP58↓,1,   GRP78/BiP↓,1,   Inflam↓,2,   p‑JNK↓,1,   MPO↓,1,   NF-kB↓,1,   ROS↓,1,   TNF-α↓,1,   UPR↓,1,   XBP-1↓,1,  
Total Targets: 14

Scientific Paper Hit Count for: JNK, c-Jun N-terminal kinase (JNK)
3 Quercetin
1 Fisetin
1 Kaempferol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:168  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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