Arsenic has been used effectively as a chemotherapeutic
drug for the treatment of
acute promyelocytic leukemia patients. Numerous studies have demonstrated that
arsenic induces apoptosis in various cell types. In the present study, we showed that approximately 35% of
arsenite-treated HeLa S3 cells arrested in mitosis. After release from
arsenite treatment, more than 80% of
arsenite-arrested mitotic cells subsequently underwent apoptosis, as indicated by anachronistic nuclear envelope reformation,
DNA ladder occurrence,
chromatin condensation, and activation of
caspases 3 and 9. In exploring how these cells entered apoptosis mechanistically, we found an inverse correlation between mitotic indexes and apoptotic frequencies. As shown by using
Percoll density gradient fractionation and flow cytometric analysis, the mitosis-mediated apoptosis induced by
arsenite was accompanied by delayed
cyclin B degradation and altered mitotic exit. Furthermore, treatment of
arsenite-arrested mitotic cells with
staurosporine or
2-aminopurine resulted in a rapid degradation of
cyclin B, moved these cells forward to interphase without cell division, and abrogated apoptosis. These results suggest that apoptosis occurs in
arsenite-arrested mitotic cells that exit mitosis abnormally.