Down-regulation of Bcl2 and Survivin, and up-regulation of Bax involved in copper (II) phenylthiosemicarbazone complex-induced apoptosis in leukemia stem-like KG1a cells

[Display omitted] •Copper (II) phenylthiosemicarbazone complex (Cu-PTSC) inhibits KG1a cell viability.•Cu-PTSC induces G0/G1 cell cycle arrest and apoptosis in KG1a cells.•Cu-PTSC down-regulates Bcl2 and Survivin, and up-regulates Bax in KG1a cells. Previous studies suggested that phenylthiosemicarbazones are considered as a new apoptosis-inducing agent. In this study, anti-proliferative and apoptotic effects of the copper (II) phenylthiosemicarbazone complex (Cu-PTSC) were investigated in human acute myeloid leukemia KG1a cell line. The KG1a cells were treated with various concentrations (20−140 μM) of the Cu-PTSC, and cell viability was determined by MTT assay. The IC50 value of 80 ± 2.5 μM was selected for further evaluations. Apoptosis, as the antitumor strategy in the cells, was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) double staining, and surface expression assay of phosphatidylserine by Annexin V/PI technique was studied via flow cytometry. Results indicated that the cells undergo morphologic changes with chromatin condensation and G0/G1 cell cycle arrest after treatment with Cu-PTSC. The presence of phosphatidylserine on the outer surface of the cell membrane confirmed the apoptosis occurrence in the KG1a cells. Real-time PCR and western blot analyses revealed that the incubation of KG1a cells with Cu-PTSC down-regulated the expression of Bcl-2 (anti-apoptotic protein) and Survivin (as an IAP protein) while induced the expression of Bax (pro-apoptotic protein). Based on present data, it seems that Cu-PTSC may provide a novel therapeutic approach for the treatment of acute myeloid leukemia.