Synergistic effect of cell differential agent-II and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells

AIM: To illustrate the possible role of cell differential agent-II (CDA-II) in the apoptosis of hepatoma cells induced by arsenic trioxide (As(2)O(3)). METHODS: Hepatoma cell lines BEL-7402 and HepG2 were treated with As(2)O(3) together with CDA-II. Cell surviving fraction was determined by MTT assay; morphological changes were observed by immunofluorescence staining of Hoechst 33,258; and cell cycle and the apoptosis index were determined by flow cytometry (FCM). RESULTS: Cytotoxicity of CDA-II was low. Nevertheless, CDA-II could strongly potentiate arsenic trioxide-induced apoptosis. At 1.0 g/L CDA-II, IC(50) of As(2)O(3) in hepatoma cell lines was reduced from 5.0 micromol/L to 1.0 micromol/L (P<0.01). The potentiation of apoptosis was dependent on the dosage of CDA-II. FCM indicated that in hepatoma, cell growth was inhibited by CDA-II at lower concentrations (<2.0 g/L) primarily by arresting at S and G(2) phase, and at higher concentrations (>2.0 g/L) apoptotic cell and cell cycle arresting at G(1) phase increased proportionally. The combination of two drugs led to much higher apoptotic rates, as compared with the either drug used alone. CONCLUSION: CDA-II can strongly potentiate As(2)O(3)-induced apoptosis in hepatoma cells, and two drugs can produce a significant synergic effect.