Resveratrol / other 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


other, other: Click to Expand ⟱
Source:
Type:
custom


Scientific Papers found: Click to Expand⟱
4664- GEN,  CUR,  RES,  EGCG,  SFN  Targeting cancer stem cells by nutraceuticals for cancer therapy
- Review, Var, NA
CSCs↓, other↝, eff↑, CD44↓, p‑STAT3↓,
3612- RES,    Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential
- Review, AD, NA
*other↑, *Aβ↓, *Inflam↓, *NF-kB↓, *neuroP↑, *HO-1↑, *lipid-P↓, *COX2↓, *AMPK↑, *Catalase↑, *SOD↑, *GSR↑, *ROS↓, *MMP9↓, *cognitive↑, *SIRT1↑, *IL1β↓, *IL6↓,
3099- RES,    Resveratrol and cognitive decline: a clinician perspective
- Review, Nor, NA - NA, AD, NA
*antiOx↑, *ROS↓, *cognitive↑, *neuroP↑, *SIRT1↑, *AMPK↑, *GPx↑, *HO-1↑, *GSK‐3β↑, *COX2↓, *PGE2↓, *NF-kB↓, *NO↓, *Casp3↓, *MMP3↓, *MMP9↓, *MMP↑, *GSH↑, *other↑, *BioAv↑, *memory↑, *GlutMet↑, *BioAv↓, *Half-Life↓, *toxicity∅,
871- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- in-vitro, BC, 4T1 - in-vivo, BC, 4T1
T-Cell↑, Neut↓, Macrophages↓, ROS↑, MMP↓, other↓, AntiTum↑, TumVol↓,
2439- RES,    By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice
- in-vitro, HCC, HCCLM3 - in-vitro, Nor, L02 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7
HK2↓, ChemoSen↑, other↑, Glycolysis↓, lactateProd↓, TumCP↓, Casp3↑, cl‑PARP↑, PKM2↓,
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↑,
881- RES,    Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein
- in-vitro, BC, MDA-MB-231 - in-vitro, PC, PANC1 - in-vitro, Pca, DU145
TumCCA↑, cycD1/CCND1↓, Bcl-xL↓, Mcl-1↓, other↓,
880- RES,    Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol
- in-vitro, BC, MDA-MB-231
other↓, TumW↓, FOXO↑, BMP2↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

OXPHOS↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics

ATP↑, 1,   MMP↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis

ECAR↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 2,   PDH↑, 1,   PKM2↓, 1,   PPP↓, 1,  

Cell Death

Bcl-xL↓, 1,   BMP2↑, 1,   Casp3↑, 1,   Mcl-1↓, 1,  

Transcription & Epigenetics

other↓, 3,   other↑, 1,   other↝, 1,  

DNA Damage & Repair

cl‑PARP↑, 1,  

Cell Cycle & Senescence

cycA1/CCNA1↑, 1,   cycD1/CCND1↓, 1,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

CD44↓, 1,   CSCs↓, 1,   FOXO↑, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration

Ca+2↝, 1,   TumCP↓, 2,  

Immune & Inflammatory Signaling

Macrophages↓, 1,   Neut↓, 1,   T-Cell↑, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   eff↑, 1,  

Functional Outcomes

AntiTum↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 40

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSR↑, 1,   HO-1↑, 2,   lipid-P↓, 1,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics

MMP↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 2,   ECAR∅, 1,   GlutMet↑, 1,   SIRT1↑, 2,  

Cell Death

Casp3↓, 1,  

Transcription & Epigenetics

other?, 1,   other↑, 2,  

Proliferation, Differentiation & Cell State

GSK‐3β↑, 1,  

Migration

MMP3↓, 1,   MMP9↓, 2,  

Angiogenesis & Vasculature

NO↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   PGE2↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↑, 1,   Half-Life↓, 1,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

cognitive↑, 2,   memory↑, 1,   neuroP↑, 2,   toxicity∅, 1,  
Total Targets: 36

Scientific Paper Hit Count for: other, other
8 Resveratrol
2 Curcumin
1 Genistein (soy isoflavone)
1 EGCG (Epigallocatechin Gallate)
1 Sulforaphane (mainly Broccoli)
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#:767  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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