Resveratrol / SOD2 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

SOD2, MnSOD: Click to Expand ⟱

Source:

Type: protein

Manganese superoxide dismutase (MnSOD, also known as SOD2).
SOD2 (Superoxide Dismutase 2) is a protein that is a member of the superoxide dismutase family of enzymes, which are involved in the detoxification of superoxide radicals.

-MnSOD is localized in the mitochondria and plays a key role in detoxifying superoxide radicals, thereby limiting oxidative damage and maintaining mitochondrial integrity.
• By modulating ROS levels, MnSOD influences cellular signaling pathways involved in proliferation, apoptosis, and metabolic adaptation—all of which are critical during tumorigenesis.

Typically low SOD2 expression in cancers, with poor prognosis.

-Increased MnSOD levels may help tumor cells manage the high levels of ROS resulting from rapid cell division and metabolic alterations, which can contribute to tumor progression.
- Some prognostic studies associate high levels of MnSOD with resistance to apoptosis and poorer patient outcomes; however, findings are not entirely consistent across all studies.

• Depending on the tumor type and the balance with other antioxidant systems, high MnSOD can be associated with either favorable or unfavorable clinical outcomes, reflecting its dual roles in cancer biology.

Scientific Papers found: Click to Expand⟱

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↑,

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:

Redox & Oxidative Stress ⓘ

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

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,

Immune & Inflammatory Signaling ⓘ

IL8↓, 1, MCP1↓, 1, p65↓, 1, TNF-α↓, 1,
Total Targets: 9

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: SOD2, MnSOD

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