Resveratrol / lactateProd 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


lactateProd, lactate production: Click to Expand ⟱
Source:
Type:
Lactate production has been linked to cancer development and progression. In normal conditions, lactate is produced in cells through a process called glycolysis, which breaks down glucose to generate energy. However, in cancer cells, this process is often upregulated, leading to increased lactate production, even in the presence of oxygen. This phenomenon is known as the Warburg effect.

-Lactate is the end product of glycolysis and induces TGFβ1 upregulation and the acidic microenvironment.


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↑,
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↓,
2439- RES,    By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice
- in-vitro, HCC, HCCLM3 - in-vitro, Nor, L02 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7
HK2↓, ChemoSen↑, other↑, Glycolysis↓, lactateProd↓, TumCP↓, Casp3↑, cl‑PARP↑, PKM2↓,
993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓, Glycolysis↓, PPP↓, ATP↑, PDH↑, Ca+2↝, TumCP↓, lactateProd↓, OCR↑, ECAR↓, *ECAR∅, *other?, cycE/CCNE↑, cycA1/CCNA1↑, TumCCA↑, cycD1/CCND1↑, OXPHOS↑,
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↓,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GPx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↓, 1,   ROS↝, 1,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics

ATP↑, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis

cMyc↓, 1,   ECAR↓, 1,   FDG↓, 1,   GlucoseCon↓, 4,   Glycolysis↓, 4,   HK2↓, 4,   lactateProd↓, 7,   PDH↑, 1,   PFK1↓, 1,   PKM2↓, 3,   PPP↓, 1,   Warburg↓, 1,  

Cell Death

Akt↓, 3,   Casp3↑, 1,   survivin↓, 1,  

Transcription & Epigenetics

other↑, 1,  

DNA Damage & Repair

cl‑PARP↑, 1,   SIRT6↑, 1,  

Cell Cycle & Senescence

cycA1/CCNA1↑, 1,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

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

Migration

Ca+2↝, 1,   Ki-67↓, 1,   MMP7↓, 1,   MMPs↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

EGFR↓, 2,   Hif1a↓, 1,  

Barriers & Transport

GLUT1↓, 3,  

Immune & Inflammatory Signaling

NF-kB↓, 1,  

Drug Metabolism & Resistance

BioEnh?, 1,   ChemoSen↑, 3,   Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers

EGFR↓, 2,   Ki-67↓, 1,  

Functional Outcomes

AntiTum↑, 1,  
Total Targets: 56

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   ROS↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis

ECAR∅, 1,  

Transcription & Epigenetics

other?, 1,  

Migration

AntiAg↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,  

Drug Metabolism & Resistance

BioAv↝, 1,   Dose↝, 1,  

Functional Outcomes

hepatoP↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 12

Scientific Paper Hit Count for: lactateProd, lactate production
7 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#:739  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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