Molecular Mechanism of Arsenic Trioxide-Induced Apoptosis in HL-60 and Cell Lines

Abstract

Recently, it has been reported that arsenic trioxide (As2 O3) is an effective anticancer agent for acute promyelocytic leukemia (APL). In the present study, we examined the anticancer effects of As2 O3 at low concentration (0.25～2.OμM) on two hunan leukemia/lymphoma cell lines, HL-60 and RL, in vitro. We found that As2 O3 inhibited the growth of HL-60 and RL similar to the reported APL cell line, NB4. Typical apoptosis was observed in morphologlcal study and DNA fragmentation assay, as well as a cell cycle arrest at subG1. To address the mechanism of As2 03-induced apoptosis, we also examined the effect of As2 O3 on the CD95/CD95L pathway and bcl-2 protein expression. The results showed that the CD95/CD95L expressions were upregulated; meanwhile, caspase 8 and caspase 3 were activated. However, the bcl-2 protein expression was downregulated. Using anti-CD95 monoclonal antibody to block the CD95 pathway, As2 O3 - induced apoptosis was ameliorated. These data suggest that in HL-60 and RL cell lines the CD95/CD95L pathway and downregulation of bc1-2 protein expression are invoIved in As2 O3-induced apoptosis.