Resveratrol / TNF-α 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↓">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↓">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


TNF-α, TNF-α: Click to Expand ⟱
Source: HalifaxProj (block)
Type:
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a complex role in cancer biology. It is primarily produced by activated macrophages and is involved in systemic inflammation. TNF-α is a pro-inflammatory cytokine that can promote inflammation, which is a known factor in cancer development.
Overall, the expression of TNF-α in cancers is often linked to inflammation, tumor progression, and the tumor microenvironment.


Scientific Papers found: Click to Expand⟱
5780- CRMs,  HCAs,  RES,  Sper,  ASA  Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
- Review, Var, NA
*OS↑, *AntiAge↑, *cardioP↑, *neuroP↑, AntiCan↑, *TNF-α↓, *Weight↓, *BP↓, *Inflam↓, *Insulin↓, *ROS↓, *AMPK↑, *mTOR↓, *SIRT1↑, CRM↑,
182- CUR,  RES,  GI,    Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
p38↓, MKP5↑, TNF-α↓, COX2↓, NF-kB↓,
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↓,
3068- RES,    Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation
- in-vitro, lymphoma, U937
p65↓, SOD2↓, Prx↓, Catalase↓, Trx↓, TNF-α↓, IL8↓, MCP1↓, SIRT1↑,
3613- RES,    Resveratrol for Alzheimer's disease
- Review, AD, NA
*SIRT1↑, *BioAv↝, *toxicity↓, *ROS↓, *antiOx↑, *Aβ↓, *MMP9↓, *TNF-α↓,
105- RES,  QC,    The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell
- in-vitro, Pca, PANC1
N-cadherin↓, TNF-α↓, ACTA2↓, EMT↓, CD133↓, CSCs↓,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,

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

Catalase↓, 1,   Prx↓, 1,   SOD2↓, 1,   Trx↓, 1,  

Mitochondria & Bioenergetics

MKP5↑, 1,  

Core Metabolism/Glycolysis

CRM↑, 1,   SIRT1↑, 1,  

Cell Death

Apoptosis↑, 1,   p38↓, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

Proliferation, Differentiation & Cell State

CD133↓, 1,   CSCs↓, 1,   EMT↓, 1,   STAT3↓, 1,  

Migration

ACTA2↓, 1,   N-cadherin↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 1,   p65↓, 1,   TNF-α↓, 4,  

Protein Aggregation

NLRP3↓, 1,  

Drug Metabolism & Resistance

eff↑, 2,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

AntiCan↑, 1,  
Total Targets: 33

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   H2O2↓, 1,   HO-1↑, 1,   mt-lipid-P↓, 1,   MDA↓, 1,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS↓, 3,  

Mitochondria & Bioenergetics

ATP↑, 1,   Insulin↓, 1,   MMP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 2,   NADH:NAD↑, 1,   PPARγ↑, 1,   SIRT1↑, 3,  

Cell Death

Cyt‑c∅, 1,  

Protein Folding & ER Stress

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State

FOXO↑, 1,   GSK‐3β↓, 1,   mTOR↓, 1,  

Migration

AntiAg↑, 1,   MMP9↓, 2,  

Barriers & Transport

BBB↓, 1,  

Immune & Inflammatory Signaling

IL1β↓, 1,   Inflam↓, 2,   NF-kB↓, 1,   p65↓, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↝, 1,   eff↑, 3,   Half-Life↝, 1,  

Clinical Biomarkers

BP↓, 2,  

Functional Outcomes

AntiAge↑, 1,   cardioP↑, 1,   motorD↑, 1,   neuroP↑, 2,   OS↑, 1,   toxicity↓, 1,   Weight↓, 1,  
Total Targets: 45

Scientific Paper Hit Count for: TNF-α, TNF-α
7 Resveratrol
1 Calorie Restriction Mimetics
1 Hydroxycinnamic-acid
1 Spermidine
1 Aspirin -acetylsalicylic acid
1 Curcumin
1 Ginger/6-Shogaol/Gingerol
1 Quercetin
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#:309  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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