Generation of reactive oxygen species by a novel berberine-bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells

摘要: Abstract 2,3-Methenedioxy-9-O-(3′α,7′α-dihydroxy-5′β-cholan-24′-propy-lester)berberine (B4) is a novel berberine–bile acid analog synthesized in our laboratory. Previously, we showed that B4 exerted greater cytotoxicity than berberine several human cancer cell lines. Therefore, further evaluated the mechanism governing its anticancer actions hepatocellular carcinoma SMMC-7721 cells. inhibited proliferation of cells, and stimulated reactive oxygen species (ROS) production mitochondrial membrane depolarization; anti-oxidant capacity was reduced. also induced release cytochrome c from mitochondria to cytosol an increase poly ADP-ribose polymerase (PARP) cleavage products, reflective caspase-3 activation. Moreover, nuclear translocation apoptosis-inducing factor (AIF) rise DNA fragmentation. Pretreatment with N-acetylcysteine (NAC) B4-mediated effects, including cytotoxicity, ROS production, depolarization intracellular Ca2+, release, PARP cleavage, AIF translocation. Our data suggest induces ROS-triggered caspase-dependent caspase-independent apoptosis pathways cells may be specific potential strategy for treating hepatic carcinoma.