Resveratrol / NLRP3 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↓">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


NLRP3, NOD-like receptor pyrin domain-containing protein 3: Click to Expand ⟱
Source:
Type:
NLRP3 (NOD-like receptor pyrin domain-containing protein 3) is a protein that plays a crucial role in the regulation of inflammation and immune responses.
NLRP3 typically has high expression in cancers, with poor prognosis.
For alzheimer's disease:
-NLRP3 is upregulated in Alzheimer's disease (AD)
-NLRP3 is activated in microglia in response to amyloid-β (Aβ) and tau aggregates.
-Promotes tau hyperphosphorylation and spread via inflammation-driven pathways.




Scientific Papers found: Click to Expand⟱
3073- RES,    Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy
- in-vitro, Nor, NA
*NLRP3↓, *mtDam↓, *p38↑,
3074- RES,    Possible therapeutic targets for NLRP3 inflammasome-induced breast cancer
- Review, BC, NA
NLRP3↓, SIRT1↑,
3075- RES,  Rad,    The Protection Effect of Resveratrol Against Radiation-Induced Inflammatory Bowel Disease via NLRP-3 Inflammasome Repression in Mice
- in-vivo, Nor, NA
*SIRT1↑, *radioP↑, *NLRP3↓, *Weight↑, *IL1β↓,
3079- RES,    Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action
- Review, Var, NA
angioG↓, TumMeta↓, ChemoSen↑, NADPH↑, SIRT1↑, NF-kB↓, NLRP3↓, Dose↝, COX2↓, MMP9↓, PGE2↓, TIMP1↑, TIMP2↑, Sp1/3/4↓, p‑JNK↓, uPAR↓, ROS↓, CXCR4↓, IL6↓, Gli1↓, *ROS↓, *GSTs↑, *SOD↑, *Catalase↑, *GPx↑, *lipid-P↓, *GSH↑, eff↑, eff↑, eff↑,
3072- RES,    Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway
- in-vitro, GBM, LN229 - in-vitro, GBM, U87MG
tumCV↓, TumCP↓, TumCMig↓, Apoptosis↑, NLRP3↓, JAK2↓, STAT3↓, IL1β↓, IL18↓, IL6↓, TNF-α↓, Inflam↓,
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↑,
3070- RES,    Resveratrol inhibits tumor progression by down-regulation of NLRP3 in renal cell carcinoma
- in-vitro, RCC, ACHN - in-vitro, RCC, 786-O - in-vivo, NA, NA
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, NLRP3↓,
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↓,
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↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

H2O2↑, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis

NADPH↑, 1,   SIRT1↑, 3,  

Cell Death

Apoptosis↑, 2,   BAX↑, 1,   p‑JNK↓, 1,   PUMA↑, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

DNA Damage & Repair

P53↑, 1,  

Proliferation, Differentiation & Cell State

Gli1↓, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 2,  

Migration

MMP9↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   uPAR↓, 1,  

Angiogenesis & Vasculature

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

Immune & Inflammatory Signaling

COX2↓, 2,   CXCR4↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 1,   JAK2↓, 1,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation

NLRP3↓, 5,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

IL6↓, 2,  

Functional Outcomes

chemoPv↑, 1,  
Total Targets: 44

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 2,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 2,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics

mtDam↓, 1,   PGC-1α↓, 1,  

Core Metabolism/Glycolysis

AMPK↑, 2,   p‑CREB↑, 1,   SIRT1↑, 3,  

Cell Death

BAX↓, 1,   Bcl-2↑, 1,   iNOS↓, 1,   p38↑, 1,  

Migration

miR-155↓, 1,   MMP9↓, 1,   PKA↑, 1,  

Immune & Inflammatory Signaling

IL1β↓, 2,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 2,  

Synaptic & Neurotransmission

BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation

Aβ↓, 1,   BACE↓, 1,   NLRP3↓, 4,   PP2A↑, 1,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

memory↑, 1,   neuroP↑, 1,   radioP↑, 1,   Weight↑, 1,  
Total Targets: 36

Scientific Paper Hit Count for: NLRP3, NOD-like receptor pyrin domain-containing protein 3
9 Resveratrol
1 Radiotherapy/Radiation
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#:908  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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