Effects of arsenic trioxide on multiple myeloma cells

Purpose:To investigate the response of multiple myeloma cells to arsenic trioxide (As 2O 3) and their possible mechanisms.Methods:Multiple myeloma derived cell lines RPMI 8226 and U266 cells were used as in vitro models. Apoptosis was assessed by morphology, flow cytometry, and DNA electrophoresis. Mitochondrial transmembrane potentials (ΔΨm) were detected by measuring cellular Rhodamine 123 staining intensity on flow cytometry. Caspase 3 activation was assessed by means of western blot.Results:Different concentrations of As 2O 3 exerted the dissimilar effects on RPMI8226 and U266 cell lines in the time dependent manner. 0.1 to 0.5 μmol/L As 2O 3 inhibited cell proliferation without apoptosis induction, 2.0 μmol/L As 2O 3 induced cell apoptosis, while 1.0 μmol/L As 2O 3 inhibited proliferation with weak apoptosis inducing effect. Futhermore,As 2O 3 induced apoptosis was parallel to the ΔΨm collapse and caspase 3 activation in the presence of intact membrane.Conclusions:As 2O 3 has a wide effect spectrum in term of apoptosis induction, and the ΔΨm collapse ia a pivotal and common mechanism for As 2O 3 induced apoptosis.