Resveratrol / DRP1/DNM1L 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


DRP1/DNM1L, DRP1 / DNM1L — mitochondrial fission regulator: Click to Expand ⟱
Source:
Type:

DRP1 / DNM1L

Item Description
Target name DRP1 / DNM1L
Full name Dynamin-related protein 1; Dynamin-1-like protein
Gene DNM1L
Primary function Core GTPase regulator of mitochondrial fission; also involved in peroxisomal division, mitosis-linked mitochondrial remodeling, mitophagy, apoptosis regulation, and mitochondrial quality control.
Target class Mitochondrial dynamics / mitochondrial fission / metabolic stress response target
Main disease logic Pathological DRP1 activation can drive excessive mitochondrial fragmentation, impaired oxidative phosphorylation, ROS production, calcium stress, mitophagy imbalance, inflammatory signaling, and cell survival adaptation.
Preferred modulation direction Inhibit excessive DRP1 activation or disrupt pathological DRP1-FIS1 signaling; avoid complete suppression of basal mitochondrial fission.
Key adaptors / related targets FIS1, MFF, MiD49, MiD51, OPA1, MFN1, MFN2, PINK1, PRKN/Parkin
Major caution DRP1 is required for normal mitochondrial maintenance, mitosis, neuronal function, and stress adaptation. Global inhibition could impair normal mitochondrial quality control.

Cancer relevance

Aspect Cancer relevance Likely Desired Direction
Proliferation Many cancer models show increased DRP1-mediated fission supporting mitochondrial redistribution, mitosis, and rapid growth. Down / inhibit excessive DRP1
Metabolic adaptation DRP1 can support metabolic remodeling, mitochondrial fragmentation, altered oxidative phosphorylation, glycolytic adaptation, and survival under stress. Down in DRP1-dependent tumors
Migration / invasion / metastasis DRP1-driven mitochondrial fission can support motility and invasive behavior by changing mitochondrial distribution and energy availability. Down
Cancer stemness / tumor-initiating cells DRP1 and the DRP1-FIS1 axis are implicated in tumor-initiating cell expansion and aggressive phenotypes in some cancers. Down
Therapy resistance Excessive mitochondrial fission may contribute to resistance to chemotherapy, radiation, oxidative stress, and apoptosis depending on tumor type. Down or context-specific
Apoptosis caveat DRP1 can also participate in apoptosis-associated mitochondrial fragmentation. Therefore, indiscriminate DRP1 blockade could theoretically reduce apoptosis in some contexts. Context-dependent
Database cancer rating High mechanistic relevance; strongest as a mitochondrial-stress, invasion, tumor stemness, and therapy-resistance target. Translational status remains preclinical. Add as cancer target

Alzheimer's disease relevance

Aspect Alzheimer's disease relevance Likely Desired Direction
Aβ toxicity Aβ has been reported to interact with DRP1 and promote excessive mitochondrial fission, ROS generation, energetic failure, and synaptic dysfunction. Down / inhibit excessive DRP1
Tau pathology Hyperphosphorylated tau is linked to abnormal mitochondrial dynamics and may worsen DRP1-associated mitochondrial fragmentation. Down
Synaptic function Excessive DRP1 activation can impair mitochondrial transport, ATP availability, and synaptic maintenance. Down
Oxidative stress DRP1-associated mitochondrial fragmentation can increase ROS and reduce mitochondrial membrane potential and respiratory efficiency. Down
Neuroinflammation Altered DRP1 activation has been linked to mitochondrial dysfunction and inflammatory signaling, including NLRP3-related pathways in AD models. Down / normalize
Therapeutic strategy Selective inhibition of pathological DRP1-FIS1 interaction, such as with P110-like strategies, is more attractive than complete DRP1 inhibition. Normalize fission
Database AD rating High mechanistic relevance; strong preclinical rationale for AD mitochondrial dysfunction, Aβ/tau toxicity, ROS, synaptic failure, and neuroinflammation. No established clinical DRP1-directed AD therapy. Add as AD target

Modulators / tool compounds

Compound / Strategy Mechanism Database Note
P110 peptide Selective inhibitor of pathological DRP1-FIS1 interaction; designed to reduce excessive fission while sparing basal fission. Useful reference tool compound; preclinical, not a general supplement or approved therapy.
Mdivi-1 Historically used as a DRP1/fission inhibitor, but has important off-target effects including mitochondrial complex I inhibition. Use cautiously in database notes; not a clean DRP1-specific probe.
Genetic DNM1L knockdown / inhibition Reduces DRP1 expression or activity and can suppress mitochondrial fission in experimental systems. Mechanistic research tool only.
Targeting DRP1-FIS1 axis Blocks a pathological receptor interaction involved in excessive fission. Probably the most attractive disease-modifying approach for AD and some cancers.

Overall conclusion

In cancer, DRP1 is mainly relevant to proliferation, invasion, tumor-initiating cells, metabolic adaptation, and therapy resistance. In Alzheimer's disease, DRP1 is mainly relevant to excessive mitochondrial fission, Aβ/tau toxicity, oxidative stress, synaptic dysfunction, energetic failure, and neuroinflammation. The preferred therapeutic logic is normalization or selective inhibition of pathological DRP1 activation, especially DRP1-FIS1 signaling, rather than complete blockade of mitochondrial fission.



Scientific Papers found: Click to Expand⟱
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 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:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

DRP1/DNM1L↑, 1,   FIS1↑, 1,   MFN2↑, 1,   OPA1↑, 1,  

Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   PGC-1α↑, 1,  

Functional Outcomes ⓘ

motorD↑, 1,  
Total Targets: 8

Scientific Paper Hit Count for: DRP1/DNM1L, DRP1 / DNM1L — mitochondrial fission regulator
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#:1487  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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