Resveratrol / PP2A 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


PP2A, serine/threonine phosphatase: Click to Expand ⟱
Source:
Type:
Protein Phosphatase 2A (PP2A) plays a critical role in Alzheimer’s disease (AD), especially in relation to tau pathology.
-PP2A dephosphorylates tau, thus reducing its toxicity.
-MID1 Negatively Regulates PP2A
-In AD, PP2A activity is decreased, leading to accumulation of hyperphosphorylated tau.
-Amyloid-β (Aβ) peptides may inhibit PP2A, indirectly promoting tau pathology.
-Aβ and tau pathologies are interconnected, and PP2A sits at a crossroads of both.

Some natural products that might upregulate PP2A:
-resveratrol
-Sodium selenate
-Berberine
-Fisetin
-Metformin (via indirect mechanisms)
Scientific Papers found: Click to Expand⟱
4289- RES,    Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells
- in-vitro, AD, NA
*antiOx↑, *p‑tau↓, *GSK‐3β↓, *CaMKII ↓, *PP2A↑, *neuroP↑,
4288- RES,    Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β
- in-vivo, AD, NA
*memory↑, *GSH↑, *ROS↓, *MDA↓, *p‑tau↓, *PI3K↑, *Akt↑, *AMPK↑, *PP2A↑, *GSK‐3β↓,
4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, *Inflam↓, *antiOx↑, *GSH↑, *HO-1↑, *iNOS↓, *BDNF↑, *p‑CREB↑, *PKA↑, *Bcl-2↑, *BAX↓, *IL1β↓, *IL6↓, *MMP9↓, *memory↑, *AMPK↑, *PGC-1α↓, *NF-kB↓, *Aβ↓, *SIRT1↑, *p‑tau↓, *PP2A↑, *lipid-P↓, *NLRP3↓, *BACE↓,
4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, *PP2A↑, *neuroP↑, *antiOx↑, COX2↓, *AntiAg↑, *SIRT1↑, *AMPK↑, *Acetyl-CoA↓, *FAO↑, *ADAM10↑, *BACE↓, *Aβ↓, *memory↑, *Inflam↓, *ROS↓,

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:


Immune & Inflammatory Signaling ⓘ

COX2↓, 1,  
Total Targets: 1

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   GSH↑, 2,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↓, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   AMPK↑, 3,   p‑CREB↑, 1,   FAO↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↑, 1,   BAX↓, 1,   Bcl-2↑, 1,   iNOS↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 2,   PI3K↑, 1,  

Migration ⓘ

AntiAg↑, 1,   MMP9↓, 1,   PKA↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↑, 1,   BDNF↑, 1,   p‑tau↓, 4,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 2,   NLRP3↓, 1,   PP2A↑, 4,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

memory↑, 3,   neuroP↑, 3,  
Total Targets: 36

Scientific Paper Hit Count for: PP2A, serine/threonine phosphatase
4 Resveratrol
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#:1371  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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