Resveratrol / AR Cancer Research Results

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


AR, androgen receptor: Click to Expand ⟱
Source: HalifaxProj(suppress signaling);CGL-Driver Genes
Type: Oncogene
Androgens play an important role in the proliferation, differentiation, maintenance and function of the prostate [1]. Intriguingly, they may also be involved in the development and progression of prostate cancer. Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen.

The prognostic significance of androgen receptor expression varies widely across different cancer types. In some cancers, high AR expression is associated with poor outcomes, while in others, it may indicate a better prognosis
High expression with poor prognosis is most common.

AR is used as a clinical biomarker for prostate therapy
Scientific Papers found: Click to Expand⟱
67- QC,  RES,    Overexpression of c-Jun induced by quercetin and resverol inhibits the expression and function of the androgen receptor in human prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
cJun↑, AR↓,
3078- RES,    The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment
- Review, Pca, NA
*ROS↓, ROS↑, DNAdam↑, Apoptosis↑, Hif1a↑, Casp3↑, Casp9↑, Cyt‑c↑, Dose↝, MMPs↓, MMP2↓, MMP9↓, EMT↓, E-cadherin↑, N-cadherin↓, AR↓,
3089- RES,    The Role of Resveratrol in Cancer Therapy
- Review, Var, NA
angioG↓, VEGF↓, EGFR↓, FGF↑, TumCMig↓, TumCI↓, TIMP1↑, MMP2↓, MMP9↓, NF-kB↓, Hif1a↓, PI3K↓, Akt↓, MAPK↓, EMT↓, AR↓,
3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, BioAv↓, Dose↑, eff↑, eff↑, Dose↑, BioAv↑, ROS↑, MMP↓, P21↑, p27↑, TumCCA↑, ChemoSen↑, COX2↓, 5LO↓, VEGF↓, IL1↓, IL6↓, IL8↓, AR↓, PSA↓, MAPK↓, Hif1a↓, Glycolysis↓, miR-21↓, PTEN↑, Half-Life↝, *IGF-1↓, *IGFBP3↑, Half-Life↓,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   MAPK↓, 2,   p27↑, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   miR-21↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   FGF↑, 1,   PI3K↓, 1,   PTEN↑, 1,  

Migration ⓘ

5LO↓, 1,   E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 2,   MMPs↓, 1,   N-cadherin↓, 1,   TIMP1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 2,   Hif1a↑, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1↓, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   ChemoSen↑, 1,   Dose↑, 2,   Dose↝, 1,   eff↑, 2,   Half-Life↓, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

AR↓, 4,   EGFR↓, 1,   IL6↓, 1,   PSA↓, 1,  
Total Targets: 52

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1↓, 1,   IGFBP3↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: AR, androgen receptor
4 Resveratrol
1 Quercetin
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#:15  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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