title: Berberine inhibits human hepatoma cell invasion without cytotoxicity in healthy hepatocytes.
abstract: Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its high hepatotoxicity. Many plant-derived agents have been accepted to effectively inhibit hepatoma cell invasion. However, the investigation that whether effectual plant-derived agents against invasive hepatoma cells exert unexpected cytotoxicity in healthy hepatocytes has been ignored. This study demonstrated that berberine exhibited significant cytotoxicity in HepG2 cells mainly through upregulation of reactive oxygen species (ROS) production but was ineffective in normal Chang liver cells. Berberine exerted anti-invasive effect on HepG2 cells through suppression of matrix metalloproteinase-9 (MMP-9) expression. Moreover, berberine could significantly inhibit the activity of PI3K-AKT and ERK pathways. Combination treatment of ERK pathway inhibitor PD98059 or AKT pathway inhibitor LY294002 and berberine could result in a synergistic reduction on MMP-9 expression along with an inhibition of cell invasion. Enhancement of ROS production by berberine had no influence on its suppressive effects on the activity of PI3K-AKT and ERK pathways, as well as MMP-9 expression and HepG2 cell invasion. In conclusion, our results suggest that berberine may be a potential alternative against invasive hepatoma cells through PI3K-AKT and ERK pathways-dependent downregulation of MMP-9 expression. This study also provides a previously neglected insight into the investigation of plant-derived agents-based therapy against tumor invasion with the consideration of damage to healthy cells.
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
authors: Bing
authors: B
authors: Liu
authors: Genshu
authors: G
authors: Wang
authors: Jie
authors: J
authors: Yang
authors: Xuediao
authors: X
authors: Pan
authors: Zhicheng
authors: Z
authors: Yang
authors: Linquan
authors: L
authors: Zang
mesh_terms: D001599:Berberine / Q000009:adverse effects / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D001599:Berberine