Induction of mitosis-mediated apoptosis by sodium arsenite in HeLaS3 cells

Arsenic has been used effectively as a chemotherapeutic drug for the treatm ent of acute promyelocytic leukemia patients. Numerous studies have demonst rated that arsenic induces apoptosis in various cell types. In the present study, we showed that similar to 35% of arsenite-treated HeLa S3 cells arre sted in mitosis. After release from arsenite treatment, more than 80% of ar senite-arrested mitotic cells subsequently underwent apoptosis, as indicate d by anachronistic nuclear envelope reformation, DNA ladder occurrence, chr omatin condensation, and activation of caspases 3 and 9. In exploring how t hese cells entered apoptosis mechanistically, we found an inverse correlati on between mitotic indexes and apoptotic frequencies. As shown by using Per coll density gradient fractionation and flow cytometric analysis, the mitos is-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 r apid degradation of cyclin B, moved these cells forward to interphase witho ut cell division, and abrogated apoptosis. These results suggest that apopt osis occurs in arsenite-arrested mitotic cells that exit mitosis abnormally . (C) 2000 Elsevier Science Inc.