Resveratrol / GSK‐3β 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


GSK‐3β, Glycogen synthase kinase (GSK)3β: Click to Expand ⟱
Source:
Type:
GSK3β is a crucial member of the Wnt/β-catenin-, hedgehog (Hh)-, notch- and c-myc-mediated major pro-oncogenic pathways, while also being a negative regulator of epithelial–mesenchymal transition (EMT). Accumulating evidence defines GSK3β as a potential therapeutic target in cancer, thus encouraging the development of GSK3β inhibitors for cancer treatment.
Glycogen synthase kinase 3 beta (GSK-3β) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis. Its expression and activity have been implicated in several types of cancer, often with varying prognostic implications.

In many cancers, decreased GSK-3β activity is associated with poor prognosis, while in others, increased activity may correlate with aggressive disease.


Scientific Papers found: Click to Expand⟱
4663- RES,    Exploring resveratrol’s inhibitory potential on lung cancer stem cells: a scoping review of mechanistic pathways across cancer models
- Review, Var, NA
*antiOx↑, *Inflam↓, *chemoPv↑, CSCs↓, Wnt↓, β-catenin/ZEB1↓, NOTCH↓, PI3K↓, Akt↓, mTOR↓, GSK‐3β↝, Snail↓, HH↓, p‑GSK‐3β↓, N-cadherin↓, EMT↓, CD133↓, CD44↓, ALDH1A1↓, OCT4↓, SOX4↓, Shh↓, Smo↓, Gli1↓, GLI2↓,
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↓,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,
6055- SeNPs,  CUR,  RES,    Latest Perspectives on Alzheimer's Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems
- NA, AD, NA
*DDS↑, *Dose↝, *p‑Akt↑, *GSK‐3β↓, *NF-kB↓, *BBB↑, *AChE↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death

Akt↓, 1,  

Proliferation, Differentiation & Cell State

ALDH1A1↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   Gli1↓, 1,   GSK‐3β↝, 1,   p‑GSK‐3β↓, 1,   HH↓, 1,   mTOR↓, 1,   NOTCH↓, 1,   OCT4↓, 1,   PI3K↓, 1,   Shh↓, 1,   Smo↓, 1,   Wnt↓, 1,  

Migration

GLI2↓, 1,   N-cadherin↓, 1,   Snail↓, 1,   SOX4↓, 1,   β-catenin/ZEB1↓, 1,  

Drug Metabolism & Resistance

eff↑, 2,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 2,   GSH↑, 1,   H2O2↓, 1,   HO-1↑, 1,   mt-lipid-P↓, 1,   MDA↓, 2,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics

ATP↑, 1,   MMP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 2,   NADH:NAD↑, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death

Akt↑, 1,   p‑Akt↑, 1,   Cyt‑c∅, 1,  

Kinase & Signal Transduction

CaMKII ↓, 1,  

Protein Folding & ER Stress

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State

FOXO↑, 1,   GSK‐3β↓, 4,   PI3K↑, 1,  

Migration

AntiAg↑, 1,   MMP9↓, 1,  

Barriers & Transport

BBB↓, 1,   BBB↑, 1,  

Immune & Inflammatory Signaling

IL1β↓, 1,   Inflam↓, 2,   NF-kB↓, 2,   p65↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission

AChE↓, 1,   p‑tau↓, 2,  

Protein Aggregation

PP2A↑, 2,  

Drug Metabolism & Resistance

BioAv↓, 1,   DDS↑, 1,   Dose↝, 1,   eff↑, 3,   Half-Life↝, 1,  

Clinical Biomarkers

BP↓, 1,  

Functional Outcomes

chemoPv↑, 1,   memory↑, 1,   motorD↑, 1,   neuroP↑, 2,  
Total Targets: 49

Scientific Paper Hit Count for: GSK‐3β, Glycogen synthase kinase (GSK)3β
5 Resveratrol
1 Selenium NanoParticles
1 Curcumin
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#:385  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

Home Page