Quercetin / DRP1/DNM1L Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- 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↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- 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 and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- 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-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


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⟱
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↓,
6422- QC,    Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells
- in-vitro, Alcohol, L02
*mt-ROS↓, *lipid-P↓, *MMP↑, *mtDam↓, *NLRP3↓, *ASC↓, *cl‑Casp1↓, *IL18↓, *IL1β↓, *GSDMD↓, *Pyro↓, *CYP2E1↓, *MFN1↓, *MFN2↓, *OPA1↓, *DRP1/DNM1L↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

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

Redox & Oxidative Stress ⓘ

CYP2E1↓, 1,   lipid-P↓, 1,   mt-ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   mtDam↓, 2,  

Cell Death ⓘ

cl‑Casp1↓, 1,   GSDMD↓, 1,   Pyro↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   IL18↓, 1,   IL1β↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Functional Outcomes ⓘ

memory↑, 1,  
Total Targets: 22

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#:140  Target#:1487  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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