Database Query Results : Resveratrol, , TIMP2

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- 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↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- 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 /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- 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- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


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⟱
3079- RES,    Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action
- Review, Var, NA
angioG↓, Resveratrol suppresses angiogenesis and metastatic markers to reverse cancer spread.
TumMeta↓,
ChemoSen↑, Resveratrol chemosensitizes chemotherapy and synergizes anti-cancer phytochemicals.
NADPH↑, Both in vitro and in vivo studies indicates that resveratrol enhances various redox enzymes activity, especially nicotinamide adenine dinucleotide phosphate (NADPH)
SIRT1↑, resveratrol effectively modulates both the cytokine and chemokine profiles in immune and endothelial cells by the upregulation of sirtuin-1 (SIRT1)
NF-kB↓, suppression of NF-κB and prevention of the activation of NOD-like receptor family (Nrf) pyrin domain containing-3 inflammasome [
NLRP3↓,
Dose↝, The optimal dose of resveratrol being around 150 mg per day is considered safe by all means.
COX2↓, Cox2 ↓; MMP9 ↓
MMP9↓,
PGE2↓, Cox1 and 2; PGE2↓
TIMP1↑, Resveratrol suppresses the PMA-induced MMP activity in HepG2 cell line, while it also upregulates tissue inhibitor proteins of MMP, namely, TIMP1 and TIMP2, in dose-dependent manner
TIMP2↑,
Sp1/3/4↓, Resveratrol mitigates the expression of SP-1 by inhibiting both phosphorylation of JNK1/2 and expression of urokinase-type plasminogen activator in Huh-7 cell line
p‑JNK↓,
uPAR↓,
ROS↓, Resveratrol attenuates the excessive ROS production and inflammatory cytokine, IL-6, and CXCR4 receptor expression by downregulating Gli-1 expression.
CXCR4↓,
IL6↓,
Gli1↓,
*ROS↓, redox imbalance may be attenuated by resveratrol via downregulating ROS production and simultaneously inducing antioxidant enzymes, GST, SOD, CAT and GPx activities in the cells
*GSTs↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*lipid-P↓, [72] observed that resveratrol treatment not only reduces lipid peroxidation but also increases GSH and GST serum levels in CCl4-treated rats as compared to the CCl4-control animals
*GSH↑,
eff↑, Resveratrol, in combination with thymoquinone (TQ), has been demonstrated to provide a synergistic antiproliferative efficacy against HCC cell lines as reported by Ismail et al.
eff↑, Curcumin, a potential anticancer phytochemical, in combination with resveratrol has been reported to trigger synergistic apoptotic effects against Hepa1–6 cells
eff↑, berberine in combination with resveratrol lowers the cell viability and cell adhesion. At low concentration, berberine significantly induces cell death while resveratrol inhibits cell migration in HepG2 cells

3086- RES,    Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3 - in-vitro, Pca, DU145
TET1↑, Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level.
TumCMig↓, Res also inhibited the migration and invasion of PCa cells
TumCI↓,
TIMP2↑, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9.
TIMP3↑,
MMP2↓,
MMP9↓,


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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ROS↓, 1,  

Core Metabolism/Glycolysis

NADPH↑, 1,   SIRT1↑, 1,  

Cell Death

p‑JNK↓, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Proliferation, Differentiation & Cell State

Gli1↓, 1,  

Migration

MMP2↓, 1,   MMP9↓, 2,   TET1↑, 1,   TIMP1↑, 1,   TIMP2↑, 2,   TIMP3↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   uPAR↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   CXCR4↓, 1,   IL6↓, 1,   NF-kB↓, 1,   PGE2↓, 1,  

Protein Aggregation

NLRP3↓, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   Dose↝, 1,   eff↑, 3,  

Clinical Biomarkers

IL6↓, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   ROS↓, 1,   SOD↑, 1,  
Total Targets: 7

Scientific Paper Hit Count for: TIMP2, Tissue Inhibitor of Metalloproteinases-2
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#:141  Target#:308  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

Home Page