Treatment with a selenium-platinum compound induced T-cell acute lymphoblastic leukemia/lymphoma cells apoptosis through the mitochondrial signaling pathway

Abstract

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability. Cell cycle distribution, apoptosis, reactive oxygen species (ROS) content and the mitochondrial membrane potential were analyzed using flow cytometry. Intracellular platinum content was detected using inductively coupled plasma mass spectrometry. Caspase activity was determined using a colorimetric assay. The expression of several proteins associated with apoptosis was analyzed using western blotting. The results of the present study demonstrated that treatment with EG-Se/Pt increased the inhibition of Jurkat and Molt-4 T-ALL/LBL cell viability compared with CDDP, and induced apoptosis and cell cycle arrest. The intracellular platinum content of T-ALL/LBL cells treated with EG-Se/Pt was increased compared with that of T-ALL/LBL cells treated with CDDP. EG-Se/Pt-induced apoptosis was mediated by caspase and ROS levels through the activation of the mitochondrial signaling pathway. The results of the present study suggest that EG-Se/Pt is a potential therapeutic candidate for the treatment of T-ALL/LBL.