Berberine / TumCI 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)


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
2700- BBR,    Cell-specific pattern of berberine pleiotropic effects on different human cell lines
- in-vitro, GBM, U343 - in-vitro, GBM, MIA PaCa-2 - in-vitro, Nor, HDFa
selectivity↑, TumCCA↑, Casp3↑, TumCI↓, TumCMig↓, N-cadherin?, DNMT1↑,
2711- BBR,    Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
TumCP↓, TumCI↓, TumCMig↓, Apoptosis↑, FGF↓, IGFBP3↑,
2709- BBR,    Berberine inhibits the glycolysis and proliferation of hepatocellular carcinoma cells by down-regulating HIF-1α
- in-vitro, HCC, HepG2
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, Glycolysis↓, Hif1a↓, GLUT1↓, HK2↓, PKM2↓, LDHA↓,
2702- BBR,    The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1
- in-vitro, Lung, A549 - in-vitro, Lung, H1975
TumCG↓, MAPK↓, FOXO3↑, TumCCA↑, TumCMig↓, TumCI↓, Sp1/3/4↓, PDK1↓, DNMT1↓, eff↑,
2694- BBR,    Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells
- in-vitro, BC, NA
IL8↓, TumCI↓, EGFR↓, MEK↓, ERK↓, TGF-β1↓, VEGF↓,
5182- BBR,    Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-κB, u-PA and MMP-2 and -9
- in-vitro, SCC, SCC4
TumCMig↓, TumCI↓, p‑JNK↝, p‑ERK↝, p‑p38↝, IKKα↝, NF-kB↝, MMP2↓, MMP9↓,
1102- BBR,    Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARα/RARβ in melanoma cells
- in-vitro, Melanoma, B16-BL6
TumCMig↓, TumCI↓, EMT↓, p‑PI3K↓, p‑Akt↓, RARα↓, RARβ↑, RARγ↑, E-cadherin↑, N-cadherin↓,
1092- BBR,    Berberine as a Potential Anticancer Agent: A Comprehensive Review
- Review, NA, NA
Apoptosis↑, TumCCA↑, TumAuto↑, TumCI↓, IL1↓, IL6↓, TNF-α↓, LDH↓, P2X7↓, proCasp1↓, Casp1↓, ASC↓,
2682- BBR,    Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions
- in-vitro, CRC, HT29 - in-vitro, CRC, SW480 - in-vitro, CRC, HCT116
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, necrosis↑, AQPs↓, PTEN↑, PI3K↓, Akt↓, p‑Akt↓, mTOR↓, p‑mTOR↓,
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↑,
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↑,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 2,   MEK↓, 1,   MMP↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   AMPK↝, 1,   Glycolysis↓, 1,   HK2↓, 1,   LDH↓, 1,   LDHA↓, 1,   PDK1↓, 1,   PKM2↓, 1,   RARα↓, 1,   RARβ↑, 1,   RARγ↑, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 2,   Apoptosis↑, 5,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp1↓, 1,   proCasp1↓, 1,   Casp3↓, 1,   Casp3↑, 1,   Casp8↑, 2,   Casp9↑, 2,   Cyt‑c↑, 2,   Fas↑, 1,   FasL↑, 1,   IAP1↓, 1,   p‑JNK↝, 1,   MAPK↓, 2,   MDM2↓, 1,   necrosis↑, 1,   P2X7↓, 1,   p‑p38↝, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↓, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNMT1↓, 1,   DNMT1↑, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   RB1↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   EMT↑, 1,   ERK↓, 2,   p‑ERK↝, 1,   FGF↓, 1,   FOXO3↑, 1,   IGFBP3↑, 1,   mTOR↓, 2,   mTOR↝, 1,   p‑mTOR↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   PTEN↑, 1,   RAS↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 3,   MMP3↓, 1,   MMP9↓, 3,   MMPs↓, 1,   N-cadherin?, 1,   N-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TGF-β1↓, 1,   TumCI↓, 11,   TumCMig↓, 8,   TumCP↓, 4,   TumMeta↓, 1,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

AQPs↓, 1,   GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   CD4+↓, 1,   COX2↓, 3,   IKKα↝, 1,   IL1↓, 2,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 1,   p‑JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 2,   NF-kB↝, 1,   PGE2↓, 2,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   ChemoSen↑, 1,   eff↑, 3,   eff↝, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   GutMicro↑, 1,   IL6↓, 2,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   RenoP↑, 1,  
Total Targets: 125

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

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

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 9

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
11 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#:324  State#:%  Dir#:%
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