title: Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin β1 signaling.
abstract: Colon cancer is associated with a poor prognosis, motivating strategies to prevent its development. An encouraging preventative strategy is the use of nutraceuticals; however, scientific verification of therapeutic functions and mechanisms of biological activity are necessary for the acceptance of dietary supplements in cancer treatment. Berberine is a benzylisoquinoline alkaloid extracted from many kinds of medicinal plants that has been extensively used as a Chinese traditional medicine. Recently, berberine has been reported to possess antitumoral activities. Among the various cellular targets of berberine is AMP-activated protein kinase (AMPK), which regulates tumor progression and metastasis. However, the specific role of berberine-induced AMPK activation and its effects on the metastatic potential of colon cancer remain largely unknown. The present study investigated berberine-induced activation of AMPK and its effects on colon cancer cell migration. Berberine decreased the migration of SW480 and HCT116 cells. We found that berberine activated AMPK in human colon cancer cell lines. Notably, berberine-induced activation of AMPK reduced the integrin β1 protein levels and decreased the phosphorylation of integrin β1 signaling targets. Knockdown of AMPKα1 subunits using small interfering RNA significantly attenuated berberine-induced downregulation of integrin β1 and inhibition of tumor cell migration. Collectively, our results suggest that berberine-induced AMPK activation inhibits the metastatic potential of colon cancer cells by decreasing integrin β1 protein levels and downstream signaling.
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Park
authors.forename: Seon-Mi
authors.initials: SM
authors.lastname: Seo
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Kim
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Ko
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Minyoung
authors.initials: M
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019012:Integrin beta1; D017382:Reactive Oxygen Species; D001599:Berberine; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human