title: The natural alkaloid berberine targets multiple pathways to induce cell death in cultured human colon cancer cells.
abstract: In the current paper, berberine, an isoquinoline alkaloid, was tested for its chemopreventive potential in colon cancer (SW480) cells. Berberine inhibited proliferation of colon cancer cells in a dose- and time-dependent manner. Interestingly, this compound exhibited minimum toxicity in normal cells at 200 μM. Berberine arrested SW480 cell cycle at G2/M phase, which was supported by induction of p21 expression. Induction of a series of biochemical events, including loss of mitochondrial membrane potential, release of cytochrome-c to cytosol, induction of Bcl-2 family proteins, caspases and cleavage of poly (ADP-ribose) polymerase (PARP), by berberine suggests its ability to induce apoptosis. In addition, berberine also inhibited inflammation, as evidenced by induction of expression of NFκB and Cox(2). Furthermore, berberine inhibited caspase-8 mediated angiogenesis, as confirmed through expression of tumor necrotic factor related apoptosis-inducing ligand (TRAIL), vascular endothelial growth factor (VEGF) and survivin. The results of the current study demonstrated that berberine has the ability to cause cell cycle arrest, induce apoptosis and inhibit inflammation in colon cancer cells. The magnitude of the effects observed suggests that berberine may be worth considering for further studies of its potential applications for improving health, either as a preventative or a potential treatment.
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticulture Sciences, Texas A&M University, College Station, TX 77845‐2119, USA.
authors.forename: Kotamballi N
authors.initials: KN
authors.lastname: Chidambara Murthy
authors.forename: Guddadarangavvanahally K
authors.initials: GK
authors.lastname: Jayaprakasha
authors.forename: Bhimanagouda S
authors.initials: BS
authors.lastname: Patil
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051336:Mitochondrial Membranes / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D001688:Biological Products; D042461:Vascular Endothelial Growth Factor A; D001599:Berberine; D053181:Caspase 8