Resveratrol / mTOR 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


mTOR, mammalian target of rapamycin: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
mTOR (mechanistic target of rapamycin) is a central regulator of cell growth, proliferation, metabolism, and survival. It is a serine/threonine kinase that integrates signals from nutrients, growth factors, and cellular energy status.
mTOR promotes protein synthesis and cell growth by activating downstream targets such as S6 kinase and 4E-BP1. In cancer, this pathway can become hyperactivated, leading to uncontrolled cell proliferation.

mTor Inhibitors:
-rapamycin (Sirolimus): classic natural product mTOR inhibitor
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
-Honokiol
Scientific Papers found: Click to Expand⟱
5780- CRMs,  HCAs,  RES,  Sper,  ASA  Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
- Review, Var, NA
*OS↑, *AntiAge↑, *cardioP↑, *neuroP↑, AntiCan↑, *TNF-α↓, *Weight↓, *BP↓, *Inflam↓, *Insulin↓, *ROS↓, *AMPK↑, *mTOR↓, *SIRT1↑, CRM↑,
3071- RES,    Resveratrol and Its Anticancer Effects
- Review, Var, NA
chemoPv↑, SIRT1↑, Hif1a↓, VEGF↓, STAT3↓, NF-kB↓, COX2↓, PI3K↓, mTOR↓, NRF2↑, NLRP3↓, H2O2↑, ROS↑, P53↑, PUMA↑, BAX↑,
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↓,
3096- RES,    Identification of potential target genes of non-small cell lung cancer in response to resveratrol treatment by bioinformatics analysis
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
TumCP↓, Apoptosis↑, Akt↓, mTOR↓, p38↑, MAPK↑, STAT3↓, ROS↑, SIRT1↑, SOX2↓,
3092- RES,    Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action
- Review, BC, MDA-MB-231 - Review, BC, MCF-7
TumCP↓, tumCV↓, TumCI↓, TumMeta↓, *antiOx↑, *cardioP↑, *Inflam↓, *neuroP↑, *Keap1↓, *NRF2↑, *ROS↓, p62↓, IL1β↓, CRP↓, VEGF↓, Bcl-2↓, MMP2↓, MMP9↓, FOXO4↓, POLD1↓, CK2↓, MMP↓, ROS↑, Apoptosis↑, TumCCA↑, Beclin-1↓, Ki-67↓, ATP↓, GlutMet↓, PFK↓, TGF-β↓, SMAD2↓, SMAD3↓, Vim?, Snail↓, Slug↓, E-cadherin↑, EMT↓, Zeb1↓, Fibronectin↓, IGF-1↓, PI3K↓, Akt↓, HO-1↑, eff↑, PD-1↓, CD8+↑, Th1 response↑, CSCs↓, RadioS↑, SIRT1↑, Hif1a↓, mTOR↓,
2334- RES,    Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy
- Review, Var, NA
GLUT1↓, GlucoseCon↓, lactateProd↓, Akt↓, mTOR↓, Dose↝, SIRT6↑, PKM2↓, HK2↓, PFK1↓, ChemoSen↑,
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↓,
2328- RES,    Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin
- in-vitro, Cerv, HeLa - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
PKM2↓, mTOR↓, GlucoseCon↓, lactateProd↓,
1490- RES,    Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues
- Review, Var, NA
TumCCA↑, ROS↑, Ca+2↑, MMP↓, ATP↓, TOP1?, P53↑, p53 Wildtype∅, Akt↓, mTOR↓, EMT↓, *BioAv↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 5,   SIRT3↑, 1,   TKT↝, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   CRM↑, 1,   G6PD↓, 1,   GlucoseCon↓, 3,   GlutMet↓, 1,   Glycolysis↓, 1,   HK2↓, 2,   lactateProd↓, 2,   LDH↓, 1,   PDH↑, 1,   PFK↓, 2,   PFK1↓, 2,   PKM2↓, 3,   POLD1↓, 1,   R5P↝, 1,   SIRT1↑, 4,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   CK2↓, 1,   MAPK↑, 1,   p38↑, 1,   PUMA↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 2,   p53 Wildtype∅, 1,   SIRT6↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 2,   EMT↓, 3,   FOXO4↓, 1,   Gli1↓, 1,   GSK‐3β↝, 1,   p‑GSK‐3β↓, 1,   HH↓, 1,   IGF-1↓, 1,   mTOR↓, 8,   NOTCH↓, 1,   OCT4↓, 1,   PI3K↓, 4,   Shh↓, 1,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 2,   TOP1?, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   Fibronectin↓, 1,   GLI2↓, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 2,   SOX4↓, 1,   talin↓, 1,   TGF-β↓, 1,   TumCI↓, 2,   TumCP↓, 3,   TumMeta↓, 1,   Vim?, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 3,   VEGF↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL1β↓, 1,   NF-kB↓, 1,   p‑NF-kB↓, 1,   PD-1↓, 1,   Th1 response↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   Ki-67↓, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoPv↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 106

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Keap1↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

Insulin↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   SIRT1↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 3,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cardioP↑, 2,   chemoPv↑, 1,   neuroP↑, 2,   OS↑, 1,   Weight↓, 1,  
Total Targets: 18

Scientific Paper Hit Count for: mTOR, mammalian target of rapamycin
9 Resveratrol
1 Calorie Restriction Mimetics
1 Hydroxycinnamic-acid
1 Spermidine
1 Aspirin -acetylsalicylic acid
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#:209  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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