Resveratrol / Akt 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


Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
3089- RES,    The Role of Resveratrol in Cancer Therapy
- Review, Var, NA
angioG↓, VEGF↓, EGFR↓, FGF↑, TumCMig↓, TumCI↓, TIMP1↑, MMP2↓, MMP9↓, NF-kB↓, Hif1a↓, PI3K↓, Akt↓, MAPK↓, EMT↓, AR↓,
3066- RES,    Resveratrol triggers ER stress-mediated apoptosis by disrupting N-linked glycosylation of proteins in ovarian cancer cells
GSK‐3β↑, Akt↓, CHOP↑, ER Stress↑, PERK↑, ATF6↑, UPR↑, GlucoseCon↓,
3061- RES,    The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
- Review, Var, NA
AhR↓, NRF2↑, *NQO1↑, *HO-1↑, *GSH↑, P53↑, Cyt‑c↑, Diablo↑, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, FOXO↑, p‑PI3K↓, p‑Akt↓, BIM↑, DR4↑, DR5↑, p27↑, cycD1/CCND1↓, SIRT1↑, NF-kB↓, ATF3↑,
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↓,
4662- RES,    A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H460
CSCs↓, CD133↓, OCT4↓, β-catenin/ZEB1↓, HER2/EBBR2↓, TumCP↓, PI3K↓, Akt↓, ALDH1A1↓, eff↑,
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↓,
3095- RES,    Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk
- in-vitro, BC, NA
TumCP↓, TumCMig↓, TumCI↓, cycD1/CCND1↓, cMyc↓, MMP2↓, MMP9↓, SOX2↓, Akt↓, STAT3↓, α-SMA↓,
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↑,
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↓,
2981- RES,    Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways
- in-vitro, Colon, HT-29 - in-vitro, Colon, SW48
TumCCA↑, p27↑, cycD1/CCND1↓, TumCP↓, IGF-1R↓, Akt↓, Wnt↓, P53↑, Apoptosis↑, Sp1/3/4↓, cl‑PARP↑, β-catenin/ZEB1↓, MDM2↓,
2440- RES,    Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway
- in-vitro, Lung, H460 - in-vivo, Lung, NA - in-vitro, Lung, H1650 - in-vitro, Lung, HCC827
AntiTum↑, Glycolysis↓, HK2↓, EGFR↓, Akt↓, ERK↓, GlucoseCon↓, lactateProd↓, TumCG↓, Ki-67↓,
2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, *BioAv↝, *Dose↝, *hepatoP↑, *neuroP↑, *AntiAg↑, *COX2↓, *antiOx↑, *ROS↓, *ROS↑, PI3K↓, Akt↓, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, NRF2↑, GPx↑, HO-1↑, BioEnh?, PTEN↑, ChemoSen↑, eff↑, mt-ROS↑, Warburg↓, Glycolysis↓, GlucoseCon↓, GLUT1↓, lactateProd↓, HK2↓, EGFR↓, cMyc↓, ROS↝, MMPs↓, MMP7↓, survivin↓, TumCP↓, TumCMig↓, TumCI↓,
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↑,
2471- RES,    Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression
- in-vivo, Diabetic, NA
*p‑PDK1↓, *p‑Akt↓, *Hif1a↓, *GLUT1↓,
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↓,
4666- RES,    Akt_signaling_pathway">Structural modification of resveratrol analogue exhibits anticancer activity against lung cancer stem cells via suppression of Akt signaling pathway
- in-vitro, Lung, H23 - in-vitro, Lung, H292 - in-vitro, Lung, A549
CSCs↓, eff↑, Akt↓, GSK‐3β↑, SOX2↓, cMyc↓, TumCCA↑, ROS↑, Apoptosis↑,

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 ⓘ

ATF3↑, 1,   GPx↑, 1,   HO-1↑, 2,   NRF2↑, 2,   ROS↑, 5,   ROS↝, 1,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 3,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 4,   GlucoseCon↓, 4,   GlutMet↓, 1,   Glycolysis↓, 2,   HK2↓, 4,   lactateProd↓, 3,   PFK↓, 1,   PFK1↓, 1,   PKM2↓, 1,   POLD1↓, 1,   SIRT1↓, 1,   SIRT1↑, 3,   SIRT2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

AhR↓, 1,   Akt↓, 14,   p‑Akt↓, 1,   Apoptosis↑, 4,   Bcl-2↓, 2,   Bcl-xL↓, 1,   BIM↑, 1,   CK2↓, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 1,   MAPK↓, 1,   MAPK↑, 1,   MDM2↓, 1,   p27↑, 2,   p38↑, 1,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↑, 1,   ER Stress↑, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 3,   p53 Wildtype∅, 1,   cl‑PARP↑, 1,   SIRT6↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 3,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   ALDH1A1↓, 2,   CD133↓, 2,   CD44↓, 2,   CSCs↓, 5,   EMT↓, 5,   ERK↓, 1,   FGF↑, 1,   FOXO↑, 1,   FOXO4↓, 1,   Gli1↓, 1,   GSK‐3β↑, 2,   GSK‐3β↝, 1,   p‑GSK‐3β↓, 1,   HH↓, 1,   IGF-1↓, 1,   IGF-1R↓, 1,   mTOR↓, 5,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 1,   OCT4↓, 2,   PI3K↓, 5,   p‑PI3K↓, 1,   PTEN↑, 2,   Shh↓, 2,   Smo↓, 1,   SOX2↓, 3,   STAT3↓, 3,   TCF↓, 1,   TOP1?, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 4,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 2,   Fibronectin↓, 1,   GLI2↓, 1,   Ki-67↓, 2,   MALAT1↓, 1,   MMP2↓, 3,   MMP7↓, 2,   MMP9↓, 3,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 2,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 2,   SOX4↓, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 6,   TumMeta↓, 1,   Vim?, 1,   Vim↓, 1,   Zeb1↓, 1,   α-SMA↓, 1,   β-catenin/ZEB1↓, 5,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 3,   Hif1a↓, 3,   VEGF↓, 4,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 1,   NF-kB↓, 4,   PD-1↓, 1,   Th1 response↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh?, 1,   ChemoSen↑, 2,   ChemoSen⇅, 1,   Dose↝, 1,   eff↑, 5,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   CRP↓, 1,   EGFR↓, 3,   HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   cardioP↑, 1,   hepatoP↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 156

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 2,   GSH↑, 2,   HO-1↑, 1,   Keap1↓, 1,   NQO1↑, 1,   NRF2↑, 1,   RNS↓, 1,   ROS↓, 3,   ROS↑, 1,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   p‑PDK1↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO1↝, 1,   PI3K↑, 1,   PTEN↑, 1,  

Migration ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   eNOS↑, 1,   Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↝, 1,   Dose↝, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoPv↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 3,   toxicity↓, 1,  
Total Targets: 36

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
17 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#:4  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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