The Anti-Leukemic Effects Of Obacunone (Oce) By Inducing Apoptosis Via Mitochondria-Mediated Pathway

This study was aimed to investigate the anti-leukemic effects of Obacunone (OCE) in human chronic myeloid leukemia cells and explore its potential mechanisms. The in vitro antitumor effects of OCE on K562, U937 and THP-1 cells were evaluated by MTT assay. Cells were treated with OCE at the concentrations of 10, 20 and 40 mu M for 24 h. Apoptosis detection was carried out by flow cytometer, and the expressions of apoptosis related proteins were assayed by western blot. The in vivo antitumor effects of OCE on K562 cells were further investigated in a xenograft nude mice model at a dose of 40 mg/kg for 21 days. OCE showed significant inhibitory effects on K562, cells with a half maximal inhibitory concentration (IC50) value of 28.9 mu M. OCE induced apoptosis in K562 cells by up-regulating the expressions of caspase-3, caspase-9 and Bax (p < 0.01), whereas down-regulating expressions of Bcl-2 (p < 0.01) with a dose-dependent manner. Expression of EVI-1 was also suppressed by treating with OCE, and OCE-induced apoptosis could be attenuated by transfecting with EVI-1 SiRNA. Furthermore, the in vivo experiments also indicated that OCE possessed significant antitumor effects (p < 0.01) in xenograft nude mice. Collectively, the results demonstrated that OCE had significant antitumor effects in human chronic myeloid leukemia K562 cells, and the mechanisms were probably related to the induction of apoptosis via mitochondria-mediated pathway. OCE is a potential apoptosis inducer that can be developed into promising antitumor drugs for the treatment of leukemia in the future.