Arsenic Trioxide Induces Oncosis in K562 Cell Line Via CD95 CD95L Pathway

Abstract

Recently it has been reported that arsenic trioxide (As203) is very effective in the treatment of acute promyelocytic leukemia (APL) by inducing apoptosis, but the molecular mechanism of its action on other leukemia remains unclear. In the present study, we tested the effect of As2 O3 at low concentration O.25-2.O μM on K562, a chronic myelogenous leukemia cell line. As2 03 inhibited the cell growth of K562 in a similar way to APL cell line NB4. Typical oncotic cell death, such as cytoplasmic swelling and swelling of organelles, was observed by morphological study and cell cycle was arrested at G2+M phases. During the treatment of As2 03, the CD95 and CD95 ligand (CD95L) expressions were upregulated, and caspase 8 and caspase 3 were activated, but bcl-2 expression was not changed. Treatment of the cells with anti-CD95 monoclonal antibody or ZVAD-fmk capable of blocking the CD95 signaling pathway ameliorated As2 03-induced oncosis. These results suggest that the induction of oncosis by As2 03 invoIves CD95/CD95L pathway in K562 and As2 03 may provide a novel therapy for leukemia other than APL.