Resveratrol / PDH 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


PDH, mitochondrial pyruvate dehydrogenase (PDH): Click to Expand ⟱
Source:
Type:
-An enzyme complex that plays a crucial role in cellular metabolism, particularly in the conversion of pyruvate to acetyl-CoA, which is then used to produce energy in the form of ATP. -Key enzyme in cellular metabolism that catalyzes the conversion of pyruvate (produced during glycolysis) into acetyl-CoA, which then enters the tricarboxylic acid (TCA) cycle in the mitochondria.
The phosphorylation state of PDH (p-PDH) broadly exists in the cancer cells.
Some cancer cells have been found to inhibit PDH activity, which can lead to increased lactate production and a shift towards glycolysis, even in the presence of oxygen. This is known as the Warburg effect.
-In cancer cells, PDH has been shown to be inhibited.
PDH expression is regulated by various transcription factors, including HIF-1α, c-Myc, and p53.
Scientific Papers found: Click to Expand⟱
2332- RES,    Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism
- Review, Var, NA
Glycolysis↓, GLUT1↓, PFK1↓, Hif1a↓, ROS↑, PDH↑, AMPK↑, TumCG↓, TumCI↓, TumCP↓, p‑NF-kB↓, SIRT1↑, SIRT3↑, LDH↓, PI3K↓, mTOR↓, PKM2↓, R5P↝, G6PD↓, TKT↝, talin↓, HK2↓, GRP78/BiP↑, GlucoseCon↓, ER Stress↑, Warburg↓, PFK↓,
993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓, Glycolysis↓, PPP↓, ATP↑, PDH↑, Ca+2↝, TumCP↓, lactateProd↓, OCR↑, ECAR↓, *ECAR∅, *other?, cycE/CCNE↑, cycA1/CCNA1↑, TumCCA↑, cycD1/CCND1↑, OXPHOS↑,

Showing Research Papers: 1 to 2 of 2

* 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 ⓘ

OXPHOS↑, 1,   ROS↑, 1,   SIRT3↑, 1,   TKT↝, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ECAR↓, 1,   G6PD↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 1,   LDH↓, 1,   PDH↑, 2,   PFK↓, 1,   PFK1↓, 1,   PKM2↓, 1,   PPP↓, 1,   R5P↝, 1,   SIRT1↑, 1,   Warburg↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↑, 1,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,   PI3K↓, 1,   TumCG↓, 2,  

Migration ⓘ

Ca+2↝, 1,   talin↓, 1,   TumCI↓, 1,   TumCP↓, 2,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

p‑NF-kB↓, 1,  

Clinical Biomarkers ⓘ

LDH↓, 1,  
Total Targets: 39

Pathway results for Effect on Normal Cells:


Core Metabolism/Glycolysis ⓘ

ECAR∅, 1,  

Transcription & Epigenetics ⓘ

other?, 1,  
Total Targets: 2

Scientific Paper Hit Count for: PDH, mitochondrial pyruvate dehydrogenase (PDH)
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#:245  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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