Resveratrol / FIS1 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


FIS1, Mitochondrial fission 1 protein: Click to Expand ⟱
Source:
Type:

FIS1 — Mitochondrial fission 1 protein
FIS1 is a mitochondrial outer-membrane fission adaptor/receptor linked to DRP1-mediated mitochondrial dynamics. In cancer, FIS1 is an emerging target because mitochondrial fission supports proliferation, survival adaptation, metastatic behavior, and tumor-initiating/stem-like phenotypes in some models. Recent TNBC evidence suggests FIS1 is required for expansion of tumor-initiating cells and that FIS1 loss suppresses TIC activity without broadly collapsing mitochondrial function, making it a potentially more selective mitochondrial dynamics target than global DRP1 inhibition.

-Often pro-tumor, Supports mitochondrial fragmentation/dynamics in stress-adapted cells

FIS1 is relevant to Alzheimer’s disease as part of the pathological mitochondrial fission program. AD models and human tissue studies show an imbalance toward mitochondrial fission, involving increased DRP1 and FIS1 and reduced fusion proteins such as MFN1, MFN2, and OPA1. Aβ and phosphorylated tau are linked to abnormal DRP1-mediated mitochondrial fragmentation, and increased DRP1/FIS1 interaction has been reported in Aβ-treated neurons and AD patient-derived fibroblasts.
-Direction: Usually increased or overactive in AD-like pathology

Natural Product Reported FIS1 / Fission Effect Evidence Strength for FIS1 Cancer Relevance Database Classification Suggested Note
Curcumin Reported to decrease FIS1 and DRP1-associated mitochondrial fission in several mitochondrial injury models. Moderate to strong Indirect; FIS1-specific cancer evidence is limited. FIS1/DRP1 mitochondrial fission down-modulator Best-supported natural product to link with FIS1, but still mostly non-cancer evidence.
EGCG Reported to decrease FIS1 or regulate the DRP1/FIS1 mitochondrial dynamics axis in neuroprotection and injury models. Moderate Indirect; stronger evidence for mitochondrial quality control than cancer-specific FIS1 targeting. Possible FIS1 down-modulator Useful to tag under mitochondrial fission, mitophagy, and oxidative-stress adaptation.
Urolithin A Reported to decrease FIS1 and DRP1 while improving mitophagy and mitochondrial quality control. Moderate Indirect; mostly neurodegeneration/mitophagy evidence. FIS1/DRP1-associated mitochondrial quality-control modulator Better classified under mitophagy and mitochondrial quality control
Melatonin Often reported to reduce pathological DRP1/FIS1-mediated mitochondrial fission, but effects can be context-dependent. Moderate Indirect; cancer relevance is complex and context-dependent. Context-dependent mitochondrial dynamics modulator “normalizes mitochondrial dynamics” rather than simple FIS1 inhibition.
Resveratrol Can reduce pathological DRP1/FIS1 fission in some injury models, but may increase Fis1/Drp1 expression in aging-repair contexts. Mixed Indirect; direction may vary by model and dose. Context-dependent FIS1/DRP1 modulator not a simple FIS1 inhibitor; more a mitochondrial dynamics normalizer.
Quercetin Associated with FIS1 targeting in omics/computational studies; direct experimental FIS1 modulation is weaker. Weak to moderate Indirect; not validated as a FIS1-targeted anticancer compound. Putative FIS1-associated modulator Suitable as a low-confidence or “possible” FIS1 link.
Sulforaphane Inhibits mitochondrial fission mainly through DRP1-related mechanisms; direct FIS1 modulation is unclear. Weak for FIS1 specifically Indirect; relevant to cancer metabolism and oxidative stress, but not FIS1-specific. Broader DRP1/fission pathway modulator mitochondrial fission rather than direct FIS1 modulation.
Berberine Reported to inhibit DRP1-mediated mitochondrial fission; FIS1 is mainly implicated as part of the pathway rather than directly modulated. Weak for FIS1 specifically Indirect; potentially relevant to cancer metabolism but not validated through FIS1. Broader DRP1/fission pathway modulator not a direct FIS1 modulator unless using a broader mitochondrial fission category.


Scientific Papers found: Click to Expand⟱
6416- CUR,  QC,  FA,  RES,  EGCG  Natural products targeting mitochondria: emerging therapeutics for age-associated neurological disorders
- Review, AD, NA
*DRP1/DNM1L↓, *FIS1↓, *MFN2↑, *OPA1↑, *DRP1/DNM1L↓, *FIS1↓, *OPA1↑, *MFN1↑, *MFN2↑, *DRP1/DNM1L↓, *FIS1↓, *MFN1↑, *MFN2↑, *memory↑, *mtDam↓, *DRP1/DNM1L↓, *FIS1↓,
6418- MEL,  RES,    Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation
- in-vivo, AD, NA
*neuroP↑, *DRP1/DNM1L↓, *FIS1↓, *ROS↓, *MMP↑, *SIRT1↑, *PGC-1α↑, *eff↑,
6423- RES,    Resveratrol Regulates Mitochondrial Biogenesis and Fission/Fusion to Attenuate Rotenone-Induced Neurotoxicity
- vitro+vivo, Park, NA
*neuroP↑, *FIS1↓, *OPA1↓, *MFN2↓, *PGC-1α↑, *ROS↓, *ATP↑, *motorD↑,
6420- RES,    Resveratrol Regulates Mitochondrial Biogenesis and Fission/Fusion to Attenuate Rotenone-Induced Neurotoxicity
- in-vivo, Park, NA
*DRP1/DNM1L↑, *FIS1↑, *OPA1↑, *MFN2↑, *motorD↑, *PGC-1α↑, *ROS↓, *ATP↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned

DRP1/DNM1L↓, 5,   DRP1/DNM1L↑, 1,   FIS1↓, 6,   FIS1↑, 1,   MFN1↑, 2,   MFN2↓, 1,   MFN2↑, 4,   OPA1↓, 1,   OPA1↑, 3,  

Redox & Oxidative Stress

ROS↓, 3,  

Mitochondria & Bioenergetics

ATP↑, 2,   MMP↑, 1,   mtDam↓, 1,   PGC-1α↑, 3,  

Core Metabolism/Glycolysis

SIRT1↑, 1,  

Drug Metabolism & Resistance

eff↑, 1,  

Functional Outcomes

memory↑, 1,   motorD↑, 2,   neuroP↑, 2,  
Total Targets: 19

Scientific Paper Hit Count for: FIS1, Mitochondrial fission 1 protein
4 Resveratrol
1 Curcumin
1 Quercetin
1 Ferulic acid
1 EGCG (Epigallocatechin Gallate)
1 Melatonin
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#:1486  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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