Database Query Results : Resveratrol, , CDK2

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


CDK2, Cyclin-dependent kinase 2: Click to Expand ⟱
Source:
Type:
(CDK2) complex is significantly over-activated in many cancers.
CDK2 (Cyclin-Dependent Kinase 2) is a serine/threonine kinase that regulates late G1 and S phase of the cell cycle.
CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation.


Scientific Papers found: Click to Expand⟱
3063- RES,    Resveratrol: A Review of Pre-clinical Studies for Human Cancer Prevention
- Review, Var, NA
*Inflam↓, Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
*antiOx↑,
*AntiAg↑,
*chemoPv↑, Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis
ChemoSen↑,
BioAv↑, Compared to other known polyphenols, such as quercetin and catechin, trans-resveratrol is well absorbed much more efficiently following oral administration to humans
Half-Life↝, Compared to resveratrol, which has a plasma half-life of 8–14 min, the metabolites have a plasma half-life of about 9.2 hours
COX2↓, there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed
cycD1/CCND1↓, Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
MMP9↓, associated with decreased COX-2 and matrix metalloprotease-9 expression and suppression of NFκB activation
NF-kB↓,
Telomerase↓, Relatively high concentrations also substantially downregulate telomerase activity
PSA↓, Resveratrol downregulates PSA by a mechanism independent of changes in AR
MAPK↑, Resveratrol treatment of various prostate cells also accompanied the activation of MAPK signaling and an increase in cellular p53
P53↑,


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

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death

MAPK↑, 1,   Telomerase↓, 1,  

DNA Damage & Repair

P53↑, 1,  

Cell Cycle & Senescence

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,  

Migration

MMP9↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   NF-kB↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors

CDK6↓, 1,  

Drug Metabolism & Resistance

BioAv↑, 1,   ChemoSen↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers

PSA↓, 1,  
Total Targets: 16

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,  

Migration

AntiAg↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Functional Outcomes

chemoPv↑, 1,  
Total Targets: 4

Scientific Paper Hit Count for: CDK2, Cyclin-dependent kinase 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#:467  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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