Resveratrol / AMPK 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


AMPK, adenosine monophosphate-activated protein kinase: Click to Expand ⟱
Source:
Type:
AMPK: guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways.

-Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation.


AMPK activators:
-metformin or AICAR
-Resveratrol: activate AMPK indirectly
-Berberine
-Quercetin: may stimulate AMPK
-EGCG: thought to activate AMPK
-Curcumin: may activate AMPK

-Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models.
-Alpha-Lipoic Acid (ALA): associated with AMPK activation
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↑,
3080- RES,    Resveratrol: A miraculous natural compound for diseases treatment
- Review, Var, NA
SIRT1↑, ROCK1↓, AMPK↑, *lipid-P↓, Aβ↓, COX2↓, angioG↓, Hif1a↓, VEGF↓,
3069- RES,    Resveratrol Inhibits NLRP3 Inflammasome-Induced Pyroptosis and miR-155 Expression in Microglia Through Sirt1/AMPK Pathway
- in-vitro, Nor, N9
*antiOx↑, *Inflam↓, *ROS↓, *NF-kB↓, *AMPK↑, *SIRT1↑, *miR-155↓, *NLRP3↓,
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↓,
3056- RES,    Less is more for cancer chemoprevention: evidence of a non-linear dose response for the protective effects of resveratrol in humans and mice
- in-vivo, Nor, NA
*AMPK↑, *P21↑, *Dose↓, *chemoPv↑,
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↓,
3100- RES,    Neuroprotective effects of resveratrol in Alzheimer disease pathology
- Review, AD, NA
*neuroP↑, *BioAv↓, *Half-Life↓, *BioAv↑, *BBB↑, *NRF2↑, *BioAv↓, *BioAv↑, *SIRT1↑, *cognitive↑, *lipid-P↓, *HO-1↑, *SOD↑, *GSH↑, *GPx↑, *G6PD↑, *PPARγ↑, *AMPK↑, *Aβ↓,
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∅,
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↓,
2443- RES,    Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review
- Review, Var, NA
*antiOx↑, *ROS↓, *PTEN↑, *Akt↓, *Catalase↑, *SOD↑, *ERK↓, *GSH↑, *AMPK↑, *FOXO1↝, *RNS↓, *Catalase↑, *cardioP↑, *PI3K↑, *eNOS↑, hepatoP↑,
2687- RES,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, NA, NA - Review, AD, NA
NF-kB↓, P450↓, COX2↓, Hif1a↓, VEGF↓, *SIRT1↑, SIRT1↓, SIRT2↓, ChemoSen⇅, cardioP↑, *memory↑, *angioG↑, *neuroP↑, STAT3↓, CSCs↓, RadioS↑, Nestin↓, Nanog↓, TP53↑, P21↑, CXCR4↓, *BioAv↓, EMT↓, Vim↓, Slug↓, E-cadherin↑, AMPK↑, MDR1↓, DNAdam↑, TOP2↓, PTEN↑, Akt↓, Wnt↓, β-catenin/ZEB1↓, cMyc↓, MMP7↓, MALAT1↓, TCF↓, ALDH↓, CD44↓, Shh↓, IL6↓, VEGF↓, eff↑, HK2↓, ROS↑, MMP↓,
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↑,
5788- RES,    Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans
- Trial, Nor, NA
*AMPK↑, *SIRT1↑, *PGC-1α↑, *BP↓, *CRM↑, *Dose↝, *mtDam↓, *ALAT↓, *hepatoP↑,
5781- RES,    Resveratrol improves health and survival of mice on a high-calorie diet
- in-vivo, Nor, NA
*AntiAge↑, *IGF-1↓, *AMPK↑, *CRM↑, *PGC-1α↑, *mtDam↓, *motorD↑, *hepatoP↑, *Dose↝,
119- UA,  CUR,  RES,    Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, p‑STAT3↓, Src↓, AMPK↑, GlutMet↑, TCA↑, glut↓,

Showing Research Papers: 1 to 17 of 17

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 2,   ROS⇅, 1,   SIRT3↑, 1,   TKT↝, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 4,   cMyc↓, 1,   CRM↑, 1,   G6PD↓, 1,   GlucoseCon↓, 1,   glut↓, 1,   GlutMet↑, 1,   Glycolysis↓, 1,   HK2↓, 2,   LDH↓, 1,   PDH↑, 1,   PFK↓, 1,   PFK1↓, 1,   PKM2↓, 1,   R5P↝, 1,   SIRT1↓, 1,   SIRT1↑, 2,   SIRT2↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   mTOR↓, 1,   Nanog↓, 1,   Nestin↓, 1,   PI3K↓, 1,   PTEN↑, 1,   Shh↓, 1,   Src↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TCF↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   MALAT1↓, 1,   MMP7↓, 1,   ROCK1↓, 1,   Slug↓, 1,   talin↓, 1,   TumCI↓, 1,   TumCP↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 3,   VEGF↓, 3,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCR4↓, 1,   IL6↓, 1,   NF-kB↓, 1,   p‑NF-kB↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen⇅, 1,   eff↑, 3,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,   LDH↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   hepatoP↑, 1,  
Total Targets: 79

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 5,   Catalase↑, 3,   GPx↑, 2,   GSH↑, 5,   GSR↑, 1,   H2O2↓, 1,   HO-1↑, 5,   lipid-P↓, 4,   mt-lipid-P↓, 1,   MDA↓, 2,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 2,   RNS↓, 1,   ROS↓, 8,   SOD↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   Insulin↓, 1,   MMP↑, 2,   mtDam↓, 2,   PGC-1α↓, 1,   PGC-1α↑, 3,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   ALAT↓, 1,   AMPK↑, 13,   p‑CREB↑, 1,   CRM↑, 2,   FAO↑, 1,   G6PD↑, 1,   GlutMet↑, 1,   NADH:NAD↑, 1,   PPARγ↑, 2,   SIRT1↑, 10,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   Cyt‑c∅, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO↑, 1,   FOXO1↝, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   IGF-1↓, 1,   mTOR↓, 1,   PI3K↑, 2,   PTEN↑, 1,  

Migration ⓘ

AntiAg↑, 2,   miR-155↓, 1,   MMP3↓, 1,   MMP9↓, 4,   PKA↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   eNOS↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 6,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

ADAM10↑, 1,   BDNF↑, 1,   p‑tau↓, 3,  

Protein Aggregation ⓘ

Aβ↓, 4,   BACE↓, 2,   NLRP3↓, 2,   PP2A↑, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 5,   BioAv↑, 3,   Dose↓, 1,   Dose↝, 2,   eff↑, 3,   Half-Life↓, 2,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   BP↓, 3,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 2,   cardioP↑, 2,   chemoPv↑, 1,   cognitive↑, 3,   hepatoP↑, 2,   memory↑, 5,   motorD↑, 2,   neuroP↑, 8,   OS↑, 1,   toxicity∅, 1,   Weight↓, 1,  
Total Targets: 100

Scientific Paper Hit Count for: AMPK, adenosine monophosphate-activated protein kinase
17 Resveratrol
1 Calorie Restriction Mimetics
1 Hydroxycinnamic-acid
1 Spermidine
1 Aspirin -acetylsalicylic acid
1 Ursolic acid
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#:9  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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