Resveratrol / TXA2 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

TXA2, thromboxane A2: Click to Expand ⟱

Source:

Type:

TXA2 is a bioactive lipid mediator primarily produced via the action of cyclooxygenases (COX-1/COX-2) and thromboxane synthase (TXA2S, gene TBXAS1), and it plays a role in regulating platelet aggregation, vasoconstriction, and cellular signaling that may contribute to tumor progression.

TXA2 is a bioactive lipid mediator that, beyond its role in platelet aggregation and vascular regulation, is involved in several tumor-promoting processes such as inflammation, angiogenesis, and metastasis. In various cancers—such as breast, prostate, colorectal, lung, ovarian, and head and neck cancers—elevated TXA2 levels or enhanced signaling have been associated with more aggressive disease and poorer clinical outcomes.

Scientific Papers found: Click to Expand⟱

2565-

RES,

https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2007.06788.x

in-vitro,

NA,

in-vivo,

NA,

mice

AntiAg↑, TXA2↑, PKCδ↑, Dose↝,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Migration ⓘ

AntiAg↑, 1, PKCδ↑, 1,

Angiogenesis & Vasculature ⓘ

TXA2↑, 1,

Drug Metabolism & Resistance ⓘ

Dose↝, 1,
Total Targets: 4

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: TXA2, thromboxane A2

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