Resveratrol / GLUT1 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


GLUT1, Glucose Transporter 1: Click to Expand ⟱
Source:
Type: protein
Also known as SLC2A1
An important hallmark in cancer cells is the increase in glucose uptake. GLUT1 is an important target in cancer treatment because cancer cells upregulate GLUT1, a membrane protein that facilitates the basal uptake of glucose in most cell types, to ensure the flux of sugar into metabolic pathways.
GLUT1 is a member of the facilitated glucose transporter family and is widely expressed in various tissues, including red blood cells, brain, and cancer cells.
GLUT1 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glucose uptake and energy production in cancer cells.
GLUT1 is a protein that facilitates the transport of glucose across cell membranes. GLUT1 plays a role in the regulation of glucose metabolism in diabetes.
GLUT1 plays a role in the regulation of glucose metabolism in diabetes.
GLUT1 is also known to be involved in the Warburg effect.
GLUTs are expressed 10–12-fold higher in cancer cells than in healthy tissues, especially in highly proliferative and malignant tumors.

Downregulators:
-Resveratrol: associated with reduced GLUT1 expression.
-Curcumin: downregulate GLUT1 in various cancer cell lines
-Quercetin: downregulating the expression and function of GLUT1.
-EGCG: suppress GLUT1 expression
-Berberine: linked to decreased expression or activity of GLUT1.
Scientific Papers found: Click to Expand⟱
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↓,
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↓,
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↓,
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↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GPx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 1,   ROS↝, 1,   mt-ROS↑, 1,   SIRT3↑, 1,   TKT↝, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

Akt↓, 2,   survivin↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

DNA Damage & Repair ⓘ

SIRT6↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 2,   PI3K↓, 2,   PTEN↑, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

MMP7↓, 1,   MMPs↓, 1,   talin↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 4,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,   p‑NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh?, 1,   ChemoSen↑, 2,   Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   LDH↓, 1,  
Total Targets: 53

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

p‑PDK1↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,  

Migration ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Dose↝, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 14

Scientific Paper Hit Count for: GLUT1, Glucose Transporter 1
5 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#:566  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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