Resveratrol / Hif1a 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


Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
3080- RES,    Resveratrol: A miraculous natural compound for diseases treatment
- Review, Var, NA
SIRT1↑, ROCK1↓, AMPK↑, *lipid-P↓, Aβ↓, COX2↓, angioG↓, Hif1a↓, VEGF↓,
3076- RES,    Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells
- Review, Var, NA
IL6↓, MMPs↓, MMP2↓, MMP9↓, BioAv↓, Half-Life↑, BioAv↑, Dose↝, angioG↓, IL10↓, VEGF↓, NF-kB↓, COX2↓, SIRT1↑, Wnt↓, cMyc↓, STAT3↓, PTEN↑, ROS↑, RadioS↑, Hif1a↓, E-cadherin↓, Vim↓, angioG↓,
3081- RES,    Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?
- Review, CRC, NA
NF-kB↓, FAK↓, Ki-67↓, MMP9↓, CSCs↓, CD44↓, CD133↓, ALDH1A1↓, EMT↓, ChemoSen↑, Hif1a↓, ITGB1↓, Inflam↓,
3082- RES,    Resveratrol Ameliorates the Malignant Progression of Pancreatic Cancer by Inhibiting Hypoxia-induced Pancreatic Stellate Cell Activation
- in-vitro, PC, PANC1 - in-vitro, PC, MIA PaCa-2 - in-vivo, NA, NA
VEGF↓, CXCL12↓, IL6↓, α-SMA↓, Hif1a↓, TumCI↓, EMT↓,
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↓,
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↑,
3064- RES,    Resveratrol Suppresses Cancer Cell Glucose Uptake by Targeting Reactive Oxygen Species–Mediated Hypoxia-Inducible Factor-1α Activation
- in-vitro, CRC, HT-29 - in-vitro, BC, T47D - in-vitro, Lung, LLC1
FDG↓, ROS↓, Hif1a↓, GLUT1↓, lactateProd↓,
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↓,
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↓,
967- RES,    Resveratrol binds and inhibits transcription factor HIF-1α in pancreatic cancer
- Analysis, PC, NA
Hif1a↓,
3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, BioAv↓, Dose↑, eff↑, eff↑, Dose↑, BioAv↑, ROS↑, MMP↓, P21↑, p27↑, TumCCA↑, ChemoSen↑, COX2↓, 5LO↓, VEGF↓, IL1↓, IL6↓, IL8↓, AR↓, PSA↓, MAPK↓, Hif1a↓, Glycolysis↓, miR-21↓, PTEN↑, Half-Life↝, *IGF-1↓, *IGFBP3↑, Half-Life↓,
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↓,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 6,   SIRT3↑, 1,   TKT↝, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 3,   cMyc↓, 2,   FDG↓, 1,   G6PD↓, 1,   GlucoseCon↓, 1,   GlutMet↓, 1,   Glycolysis↓, 2,   HK2↓, 2,   lactateProd↓, 1,   LDH↓, 1,   PDH↑, 1,   PFK↓, 2,   PFK1↓, 1,   PKM2↓, 1,   POLD1↓, 1,   R5P↝, 1,   SIRT1↓, 1,   SIRT1↑, 5,   SIRT2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   CK2↓, 1,   MAPK↓, 2,   p27↑, 1,   PUMA↑, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   ALDH1A1↓, 1,   CD133↓, 1,   CD44↓, 2,   CSCs↓, 3,   EMT↓, 5,   FGF↑, 1,   FOXO4↓, 1,   IGF-1↓, 1,   mTOR↓, 3,   Nanog↓, 1,   Nestin↓, 1,   PI3K↓, 4,   PTEN↑, 3,   Shh↓, 1,   STAT3↓, 3,   TCF↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

5LO↓, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   Fibronectin↓, 1,   ITGB1↓, 1,   Ki-67↓, 2,   MALAT1↓, 1,   MMP2↓, 3,   MMP7↓, 1,   MMP9↓, 4,   MMPs↓, 1,   ROCK1↓, 1,   Slug↓, 2,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   talin↓, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TumCI↓, 4,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Vim?, 1,   Vim↓, 2,   Zeb1↓, 1,   α-SMA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   EGFR↓, 1,   Hif1a↓, 12,   VEGF↓, 9,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CRP↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 5,   p‑NF-kB↓, 1,   PD-1↓, 1,   PSA↓, 1,   Th1 response↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 2,   ChemoSen↑, 2,   ChemoSen⇅, 1,   Dose↑, 2,   Dose↝, 1,   eff↑, 4,   Half-Life↓, 1,   Half-Life↑, 1,   Half-Life↝, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 2,   CRP↓, 1,   EGFR↓, 1,   IL6↓, 4,   Ki-67↓, 2,   LDH↓, 1,   PSA↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoPv↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 144

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Keap1↓, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

p‑PDK1↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

p‑Akt↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1↓, 1,   IGFBP3↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   memory↑, 1,   neuroP↑, 2,  
Total Targets: 18

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
13 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#:143  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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