Berberine / AMPK 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)


AMPK, adenosine monophosphate-activated protein kinase: Click to Expand ⟱
Source:
Type:
AMPK: guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways.

-Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation.


AMPK activators:
-metformin or AICAR
-Resveratrol: activate AMPK indirectly
-Berberine
-Quercetin: may stimulate AMPK
-EGCG: thought to activate AMPK
-Curcumin: may activate AMPK

-Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models.
-Alpha-Lipoic Acid (ALA): associated with AMPK activation
Scientific Papers found: Click to Expand⟱
2714- BBR,    Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer
AMPK↑, ITGB1↓,
2698- BBR,    A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine
- Analysis, BC, MDA-MB-231
HDAC↓, Akt↓, mTOR↓, ER Stress↑, TumAuto↑, AMPK↑, mTOR∅, HDAC∅, ac‑α-tubulin↑,
2696- BBR,    Berberine regulates proliferation, collagen synthesis and cytokine secretion of cardiac fibroblasts via AMPK-mTOR-p70S6K signaling pathway
- in-vivo, Nor, NA
*α-SMA↓, *TGF-β1↓, *IL10↑, *p‑AMPK↑, *p‑mTOR↓, *P70S6K↓, *cardioP↑,
2686- BBR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Nor, NA
Inflam↓, IL6↓, MCP1↓, COX2↓, PGE2↓, MMP2↓, MMP9↓, DNAdam↑, eff↝, Telomerase↓, Bcl-2↓, AMPK↑, ROS↑, MMP↓, ATP↓, p‑mTORC1↓, p‑S6K↓, ERK↓, PI3K↓, PTEN↑, Akt↓, Raf↓, MEK↓, Dose↓, Dose↑, selectivity↑, TumCCA↑, eff↑, EGFR↓, Glycolysis↓, Dose?, p27↑, CDK2↓, CDK4↓, cycD1/CCND1↓, cycE/CCNE↓, Bax:Bcl2↑, Casp3↑, Casp9↑, VEGFR2↓, ChemoSen↑, eff↑, eff↑, PGE2↓, JAK2↓, STAT3↓, CXCR4↓, CCR7↓, uPA↓, CSCs↓, EMT↓, Diff↓, CD133↓, Nestin↓, n-MYC↓, NOTCH↓, SOX2↓, Hif1a↓, VEGF↓, RadioS↑,
5179- BBR,    Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy
- Review, Var, NA
AMPK↑, Casp3↑, cl‑PARP↑, Mcl-1↓, cFLIP↓, β-catenin/ZEB1↓, Wnt↓, STAT3↓, mTOR↓, Hif1a↓, NF-kB↓, SIRT1↑, DNMT1↓, DNMT3A↓, miR-29b↓, IGFBP1↑, eff↑, chemoPv↑, BioAv↓,
5176- BBR,    Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice
- vitro+vivo, CRC, HCT116 - in-vitro, CRC, SW480 - in-vitro, CRC, LoVo
TumVol↓, Ki-67↓, COX2↓, AMPK↑, mTOR↓, NF-kB↓, cycD1/CCND1↓, survivin↓, P53↑, cl‑Casp3↑, TumCP↓, Inflam↓, COX2↓, ACC↑,
1395- BBR,    Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation
- in-vitro, GC, NA
Apoptosis↑, ROS↑, MMP↓, ATP↓, AMPK↑, TP53↑, p‑MAPK↓, p‑ERK↓,
2678- BBR,    Berberine as a Potential Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
*Inflam↓, *antiOx↑, *cardioP↑, *neuroP↑, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, CDC2↓, AMPK↝, mTOR↝, Casp8↑, Casp9↑, Cyt‑c↑, TumCMig↓, TumCI↓, EMT↓, MMPs↓, E-cadherin↓, Telomerase↓, *toxicity↓, GRP78/BiP↓, EGFR↓, CDK4↓, COX2↓, PGE2↓, p‑JAK2↓, p‑STAT3↓, MMP2↓, MMP9↓, GutMicro↑, eff↝, *BioAv↓, BioAv↑,
2677- BBR,    Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring
- in-vivo, Diabetic, NA
*hepatoP↑, *LC3II↑, *Beclin-1↑, *AMPK↑, *mTOR↑, *ER Stress↓, *CHOP↓, *JNK↓, *ROS↓, *Inflam↓, *BG↓, *SOD↑, *GPx↑, *Catalase↑, *IL10↑, *IL6↓, *TNF-α↓, *ALAT↓, *AST↓, *ALP↓,
2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, AntiCan↑, Apoptosis↑, TumAuto↑, TumCCA↑, TumMeta↓, TumCI↓, eff↑, eff↑, CD4+↓, TNF-α↓, IL1↓, BioAv↓, BioAv↓, other↓, AMPK↑, MAPK↓, NF-kB↓, IL6↓, MCP1↓, PGE2↓, COX2↓, *ROS↓, *antiOx↑, *GPx↑, *Catalase↑, AntiTum↑, TumCP↓, angioG↓, Fas↑, FasL↑, ROS↑, ATM↑, P53↑, RB1↑, Casp9↑, Casp8↑, Casp3↓, BAX↑, Bcl-2↓, Bcl-xL↓, IAP1↓, XIAP↓, survivin↓, MMP2↓, MMP9↓, CycB/CCNB1↓, CDC25↓, CDC25↓, Cyt‑c↑, MMP↓, RenoP↑, mTOR↓, MDM2↓, LC3II↑, ERK↓, COX2↓, MMP3↓, TGF-β↓, EMT↑, ROCK1↓, FAK↓, RAS↓, Rho↓, NF-kB↓, uPA↓, MMP1↓, MMP13↓, ChemoSen↑,
2671- BBR,    Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action
- in-vivo, Diabetic, NA
*BioAv↓, *Half-Life↝, *OCR↓, *AMPK↑,
2670- BBR,    Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
- Review, Var, NA
*Inflam↓, *antiOx↑, *Ca+2↓, *BioAv↓, *BioAv↑, *BioAv↑, *angioG↑, *MAPK↓, *AMPK↓, *NF-kB↓, VEGF↓, PI3K↓, Akt↓, MMP2↓, Bcl-2↓, ERK↓,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   CDC2↓, 1,   CDC25↓, 2,   MEK↓, 1,   MMP↓, 3,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 7,   AMPK↝, 1,   Glycolysis↓, 1,   p‑S6K↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 2,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp3↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp8↑, 2,   Casp9↑, 3,   cFLIP↓, 1,   Cyt‑c↑, 2,   Fas↑, 1,   FasL↑, 1,   IAP1↓, 1,   MAPK↓, 1,   p‑MAPK↓, 1,   Mcl-1↓, 1,   MDM2↓, 1,   p27↑, 1,   survivin↓, 2,   Telomerase↓, 2,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↓, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNAdam↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   P53↑, 2,   cl‑PARP↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 2,   RB1↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CSCs↓, 1,   Diff↓, 1,   EMT↓, 2,   EMT↑, 1,   ERK↓, 3,   p‑ERK↓, 1,   HDAC↓, 1,   HDAC∅, 1,   IGFBP1↑, 1,   mTOR↓, 4,   mTOR↝, 1,   mTOR∅, 1,   p‑mTORC1↓, 1,   n-MYC↓, 1,   Nestin↓, 1,   NOTCH↓, 1,   PI3K↓, 2,   PTEN↑, 1,   RAS↓, 1,   SOX2↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   FAK↓, 1,   ITGB1↓, 1,   Ki-67↓, 1,   miR-29b↓, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 4,   MMP3↓, 1,   MMP9↓, 3,   MMPs↓, 1,   Rho↓, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   uPA↓, 2,   ac‑α-tubulin↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 2,   Hif1a↓, 2,   VEGF↓, 2,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

CCR7↓, 1,   CD4+↓, 1,   COX2↓, 6,   CXCR4↓, 1,   IL1↓, 1,   IL6↓, 2,   Inflam↓, 3,   JAK2↓, 1,   p‑JAK2↓, 1,   MCP1↓, 2,   NF-kB↓, 4,   PGE2↓, 4,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 1,   ChemoSen↑, 2,   Dose?, 1,   Dose↓, 1,   Dose↑, 1,   eff↑, 6,   eff↝, 2,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   GutMicro↑, 1,   IL6↓, 2,   Ki-67↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   chemoPv↑, 1,   RenoP↑, 1,   TumVol↓, 1,  
Total Targets: 139

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 2,   GPx↑, 2,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↓, 1,   AMPK↑, 2,   p‑AMPK↑, 1,  

Cell Death ⓘ

JNK↓, 1,   MAPK↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   ER Stress↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↑, 1,   p‑mTOR↓, 1,   P70S6K↓, 1,  

Migration ⓘ

Ca+2↓, 1,   TGF-β1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL10↑, 2,   IL6↓, 1,   Inflam↓, 3,   NF-kB↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 2,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BG↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   hepatoP↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 40

Scientific Paper Hit Count for: AMPK, adenosine monophosphate-activated protein kinase
12 Berberine
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#:9  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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