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


TIMP2, Tissue Inhibitor of Metalloproteinases-2: Click to Expand ⟱
Source:
Type:
TIMP-2 has been shown to have distinct effects on cancer progression compared to TIMP-1. Research has suggested that TIMP-2 may have anti-tumor effects in certain types of cancer, including:
• Inhibiting tumor growth: TIMP-2 has been shown to inhibit the growth of tumor cells in vitro and in vivo.
High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers.
High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers.
High TIMP-2 expression: Breast, Lung, colorectal, Prostrate.
Low TIMP-2 expression: Ovarian, Pancreatic, Gastric.
Scientific Papers found: Click to Expand⟱
3371- QC,    Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/β-Catenin and Akt/NF-κB signaling pathways
- in-vitro, GBM, T98G
TIMP2↑, MMP2, and MMP9 was significantly decreased by quercetin treatment, while TIMP1 and TIMP2 were upregulated (
TumCG↓, Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle
TumCMig↓,
Apoptosis↑,
TumCCA↑,
MMP↓, collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process
ROS↑,
Bax:Bcl2↑,
cl‑Casp9↑,
cl‑Casp3↑,
DNAdam↑, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), γH2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression
γH2AX↑,
MGMT↓,
cl‑PARP↑,

3347- QC,    Recent Advances in Potential Health Benefits of Quercetin
- Review, Var, NA - Review, AD, NA
*antiOx↑, Its strong antioxidant properties enable it to scavenge free radicals, reduce oxidative stress, and protect against cellular damage.
*ROS↓,
*Inflam?, Quercetin’s anti-inflammatory properties involve inhibiting the production of inflammatory cytokines and enzymes,
TumCP↓, exhibits anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis.
Apoptosis↑,
*cardioP↑, cardiovascular benefits such as lowering blood pressure, reducing cholesterol levels, and improving endothelial function
*BP↓, Quercetin‘s ability to reduce blood pressure was also supported by a different investigation
TumMeta↓, The most important impact of quercetin is its ability to inhibit the spread of certain cancers including those of the breast, cervical, lung, colon, prostate, and liver
MDR1↓, quercetin decreased the expression of genes multidrug resistance protein 1 and NAD(P)H quinone oxidoreductase 1 and sensitized MCF-7 cells to the chemotherapy medication doxorubicin
NADPH↓,
ChemoSen↑,
MMPs↓, Inhibiting CT26 cells’ migration and invasion abilities by inhibiting their expression of tissue inhibitors of metalloproteinases (TIMPs) inhibits their invasion and migration abilities
TIMP2↑,
*NLRP3↓, inhibited NLRP3 by acting on this inflammasome
*IFN-γ↑, quercetin significantly upregulates the gene expression and production of interferon-γ (IFN-γ), which is obtained from T helper cell 1 (Th1), and downregulates IL-4, which is obtained from Th2.
*COX2↓, quercetin is known to decrease the production of inflammatory molecules COX-2, nuclear factor-kappa B (NF-κB), activator protein 1 (AP-1), mitogen-activated protein kinase (MAPK), reactive nitric oxide synthase (NOS), and reactive C-protein (CRP)
*NF-kB↓,
*MAPK↓,
*CRP↓,
*IL6↓, Quercetin suppressed the production of inflammatory cytokines such as IL-6, TNF-α, and IL-1β via upregulating TLR4.
*TNF-α↓,
*IL1β↓,
*TLR4↑,
*PKCδ↓, Quercetin employed suppression on the phosphorylation of PKCδ to control the PKCδ–JNK1/2–c-Jun pathway.
*AP-1↓, This pathway arrested the accumulation of AP-1 transcription factor in the target genes, thereby resulting in reduced ICAM-1 and inflammatory inhabitation
*ICAM-1↓,
*NRF2↑, Quercetin overexpressed Nrf2 and targeted its downstream gene, contributing to increased HO-1 levels responsible for the down-regulation of TNF-α, iNOS, and IL-6
*HO-1↑,
*lipid-P↓, Quercetin acts as a potent antioxidant by scavenging ROS, inhibiting lipid peroxidation, and enhancing the activity of antioxidant enzymes
*neuroP↑, This helps to counteract oxidative stress and protect against neurodegenerative processes that contribute to AD
*eff↑, rats treated with chronic rotenone or 3-nitropropionic acid showed enhanced neuroprotection when quercetin and fish oil were taken orally
*memory↑, Both memory and learning abilities in the test animals increased
*cognitive↑,
*AChE↓, The increase in AChE activity brought on by diabetes was prevented in the cerebral cortex and hippocampus by quercetin at a level of 50 mg/kg body weight.
*BioAv↑, consumption of fried onions compared to black tea, suggesting that the form of quercetin present in onions is better absorbed than that in tea
*BioAv↑, This suggests that dietary fat can increase the absorption of quercetin [180]
*BioAv↑, potential of liposomes to enhance the bioactivity and bioavailability of quercetin has been the subject of several investigations
*BioAv↑, several emulsion types that may be employed to encapsulate quercetin, but oil-in-water (O/W) emulsions are the most widely utilized.
*BioAv↑, the kind of oil (triglyceride oils made up of either long-chain or medium-chain fatty acids) affected the bioaccessibility of quercetin and gastrointestinal stability, emphasizing the significance of picking a suitable oil phase


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
Apoptosis↑,2,   Bax:Bcl2↑,1,   cl‑Casp3↑,1,   cl‑Casp9↑,1,   ChemoSen↑,1,   DNAdam↑,1,   MDR1↓,1,   MGMT↓,1,   MMP↓,1,   MMPs↓,1,   NADPH↓,1,   cl‑PARP↑,1,   ROS↑,1,   TIMP2↑,2,   TumCCA↑,1,   TumCG↓,1,   TumCMig↓,1,   TumCP↓,1,   TumMeta↓,1,   γH2AX↑,1,  
Total Targets: 20

Results for Effect on Normal Cells:
AChE↓,1,   antiOx↑,1,   AP-1↓,1,   BioAv↑,5,   BP↓,1,   cardioP↑,1,   cognitive↑,1,   COX2↓,1,   CRP↓,1,   eff↑,1,   HO-1↑,1,   ICAM-1↓,1,   IFN-γ↑,1,   IL1β↓,1,   IL6↓,1,   Inflam?,1,   lipid-P↓,1,   MAPK↓,1,   memory↑,1,   neuroP↑,1,   NF-kB↓,1,   NLRP3↓,1,   NRF2↑,1,   PKCδ↓,1,   ROS↓,1,   TLR4↑,1,   TNF-α↓,1,  
Total Targets: 27

Scientific Paper Hit Count for: TIMP2, Tissue Inhibitor of Metalloproteinases-2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:308  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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