Berberine / DRP1/DNM1L Cancer Research Results

BBR, Berberine: Click to Expand ⟱
Features:

Berberine — Berberine is a protoberberine/isoquinoline alkaloid natural product found in plants such as Coptis, Berberis, and Phellodendron. It is a small-molecule phytochemical with pleiotropic metabolic, anti-inflammatory, and anticancer signaling effects rather than a single highly selective target profile. Its standard abbreviation is BBR. In oncology it is best classified as a multitarget natural-product lead compound and adjunct-sensitizer candidate, with strong preclinical evidence but no established standard anticancer regulatory use. Its translational profile is shaped by very low conventional oral bioavailability, extensive first-pass metabolism, broad tissue distribution, and substantial context dependence between cancer-cell pro-death effects and normal-cell cytoprotective redox effects.

Primary mechanisms (ranked):

  1. AMPK-centered metabolic stress with mitochondrial dysfunction, ATP depletion, and apoptosis/autophagy induction
  2. Suppression of aerobic glycolysis and hypoxia signaling, including HIF-1α, GLUT1, HK2, LDHA, and PKM2-linked tumor metabolism
  3. Anti-proliferative cell-cycle control with cyclin/CDK suppression and tumor suppressor reactivation
  4. Inhibition of PI3K/AKT, MAPK/ERK, JAK/STAT, and NF-κB inflammatory-survival signaling
  5. Anti-metastatic and anti-EMT activity via Wnt/β-catenin, TGF-β/Smad, FAK/RhoA/ROCK, MMPs, and CXCR4-related programs
  6. Pro-oxidant mitochondrial ROS elevation and ER-stress/caspase signaling in many cancer models, with opposite antioxidant/NRF2-supportive effects in some normal-cell and non-cancer settings
  7. Context-dependent chemosensitization and radiosensitization, including effects on hypoxia signaling and DNA-repair competence
  8. Emerging ferroptosis-related activity in some tumor models, but not a universal dominant mechanism across berberine biology

Bioavailability / PK relevance: Conventional oral berberine has poor systemic bioavailability, often cited as below 1% in animal studies, because of limited absorption, P-glycoprotein efflux, first-pass intestinal/hepatic metabolism, and self-aggregation. Human exposure is usually in the low ng/mL plasma range with conventional dosing, while multiple metabolites may contribute to activity. Tissue distribution can exceed plasma levels, but PK remains a major clinical translation constraint.

In-vitro vs systemic exposure relevance: Many anticancer in-vitro studies use roughly 10–100 µM, commonly around 20–50 µM, which usually exceeds readily achievable conventional plasma exposure after standard oral dosing. Therefore, direct translation of cell-culture potency to systemic monotherapy expectations is limited unless local gut exposure, tissue accumulation, metabolite contribution, formulation enhancement, or combination use is specifically relevant.

Clinical evidence status: Strong preclinical and mechanistic evidence; limited early human oncology/chemoprevention evidence; no established phase III anticancer efficacy standard and no mainstream regulatory approval as an anticancer drug. Current clinical relevance is best viewed as investigational and adjunct-oriented rather than proven standalone oncology therapy.

Berberine is a chemical found in some plants like European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Berberine is a bitter-tasting and yellow-colored chemical.
Coptis (commonly referring to Coptidis Rhizoma, a traditional Chinese medicinal herb) contains bioactive alkaloids (most notably berberine and coptisine) that have been studied for their pharmacological effects—including their influence on reactive oxygen species (ROS) and related pathways.

– Berberine is known for its relatively low oral bioavailability, often cited at less than 1%. This low bioavailability is mainly due to poor intestinal absorption and active efflux by transport proteins such as P-glycoprotein.
– Despite the low bioavailability, berberine is still pharmacologically active, and its metabolites may also contribute to its overall effects.

• Effective Dosage in Studies
– Many clinical trials or preclinical studies use dosages in the range of 500 to 1500 mg per day, typically administered in divided doses.
– Therefore, to obtain a bioactive dose of berberine, supplementation in a standardized extract form is necessary.

-IC50 in cancer cell lines: Approximately 10–100 µM (commonly around 20–50 µM in many models)
-IC50 in normal cell lines: Generally higher (often above 100 µM), although this can vary with cell type
- In vivo studies: Dosing regimens in animal models generally range from about 50 to 200 mg/kg
- very effective AChE inhibitor (Alzheimers)
- Berberine may enhance the effects of blood-thinning medications like warfarin and aspirin.


-Note half-life reports vary 2.5-90hrs?.
-low solubility of apigenin in water : BioAv
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, EZH2↓, P53↑, HSP↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, CD133↓, β-catenin↓, n-myc↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, α↓, 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 / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 AMPK → mTOR axis ↑ AMPK / ↓ mTOR signaling Metabolic stress + growth suppression In vivo/in vitro colon tumorigenesis model: berberine activates AMPK, inhibits mTOR signaling and reduces proliferation/tumorigenesis, growth suppression, autophagy, HIF-1α ↓, glycolysis ↓, berberine’s known mitochondrial/energetic effects (ref)
2 Mitochondrial dysfunction / ROS generation ↑ ROS / mitochondrial stress Upstream metabolic trigger Berberine inhibits mitochondrial function, increases ROS, and contributes to AMPK activation and downstream apoptosis (ref)
3 Mitochondrial apoptosis (cytochrome c release) ↑ cytochrome c release Intrinsic death signaling Oral cancer model: berberine reduces mitochondrial membrane potential, releases cytochrome c, activates caspase-3 (ref)
4 Intrinsic apoptosis (caspase-3 activation) ↑ caspase-3 activation Programmed cell death Same oral cancer study documents caspase-3 activation as a key execution marker (ref)
5 NF-κB signaling (p65 activation) ↓ NF-κB activation Reduced pro-survival transcription Colon cancer model reports inhibition of p65 phosphorylation; interpreted as secondary to metabolic/redox stress (ref)
6 Cell cycle control ↑ G1 arrest Proliferation blockade Prostate cancer model: berberine induces G1-phase cell cycle arrest and caspase-3–dependent apoptosis (ref)
7 Hypoxia / glycolysis signaling (HIF-1α) ↓ HIF-1α protein Warburg / glycolysis suppression Berberine suppresses mTOR and reduces HIF-1α protein expression downstream of AMPK activation (ref)
8 Angiogenesis signaling (HIF-1α → VEGF axis) ↓ VEGF signaling Reduced vascular support Lung cancer study: berberine suppresses VEGF signaling alongside HIF-1α inhibition (ref)
9 PI3K–AKT–mTOR signaling ↓ PI3K / AKT / mTOR Survival pathway suppression Gastric cancer paper: berberine represses PI3K/AKT/mTOR signaling and improves chemosensitivity (ref)
10 Migration / invasion programs ↓ migration & invasion Anti-metastatic phenotype Tongue SCC model: berberine suppresses migration and invasion with associated signaling changes (ref)
11 Telomerase (hTERT) / immortalization axis ↓ hTERT-related signaling Reduced proliferative capacity Lung cancer study includes AP-2/hTERT regulatory axis modulation by berberine (ref)
12 In vivo tumor suppression ↓ tumorigenesis Demonstrated anti-tumor effect Colon tumorigenesis model confirms reduced proliferation and tumor burden with berberine (ref)


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⟱
6424- BBR,    Berberine Protects Glomerular Podocytes via Inhibiting Drp1-Mediated Mitochondrial Fission and Dysfunction
- in-vivo, Nor, NA
*mt-ROS↓, *DRP1/DNM1L↓,

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,  

Redox & Oxidative Stress ⓘ

mt-ROS↓, 1,  
Total Targets: 2

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#:41  Target#:1487  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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