investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As 2O 3) and their possible mechanisms Methods Two MM derived cell lines RPMI8226 and U266 cells were used as in vitro models Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity Protein expression was analyzed using Western blot Results Zero point one to 0 5?μmol/L As 2O 3 inhibited cell proliferation and 2.0?μmol/L As 2O 3 induced cell apoptosis, while 1.0?μmol/L As 2O 3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines As 2O 3 induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase 3 activation in the presence of intact membrane Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond reducing agent dithiothreitol partially antagonized As 2O 3 induced △Ψm collapse and apoptosis in MM cells All trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As 2O 3 Conclusion As 2O 3 exerts apoptosis inducing and growth inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As 2O 3 for apoptosis induction investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As 2 O 3) and their possible mechanisms Methods Two MM derived cell lines RPMI8226 and U266 cells were used as in vitro models of Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis Mitochondrial transmembrane potentials (△ Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity Protein expression was analyzed using a Western blot Results Zero point one to 0 5 μmol / L As 2 O 3 inhibited cell proliferation and 2.0 μmol / L As 2 O 3 induced cell apoptosis, while 1.0? Μmol / L As 2 O 3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines As 2O 3 induced apoptosis was accompanied by mitochondrial transmembrane potentials (△ Ψm) collapse and caspase 3 activation in the presence of intact membrane Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond reducing agent dithiothr eitol partially antagonized As 2 O 3 induced △ Ψm collapse and apoptosis in MM cells All trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As 2O 3 Conclusion As 2O 3 exerts apoptosis inducing and growth inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As 2 O 3 for apoptosis induction