Arsenic disulfide induces apoptosis of human diffuse large B cell lymphoma cells involving Bax cleavage.

The aim of the present study was to investigate the effect of arsenic disulfide (As2S2) on the proliferation and apoptosis of LY1 and LY8 human diffuse large B cell lymphoma (DLBCL) cells in an attempt to discover a more effective alternative therapy scheme. Human DLBCL cells LY1 and LY8 were treated with various concentrations of As2S2 for different time periods. Cell viability was detected by the CCK-8 assay; cell apoptosis was evaluated by flow cytometric analysis. The expression levels of Bax, Bcl-2 and caspase-3 were examined by quantitative PCR and western blotting. We found that the DLBCL cell viability was significantly decreased following treatment with As2S2 for 24, 48 and 72 h. Along with increasing As2S2 concentrations, the DLBCL cell viability was notably reduced when compared with the control group, and the results were statistically significant. Meanwhile, the apoptotic rates of DLBCL cells were significantly enhanced at 24, 48 and 72 h following treatment with increasing As2S2 concentration, and the results were also statistically significant. The quantitative PCR results showed that at the mRNA level, the Bax/Bcl-2 expression ratio was increased and caspase-3 mRNA expression was upregulated in As2S2-treated DLBCL cells. Western blot analysis revealed that at the protein level, As2S2 increased the Bax/Bcl-2 protein ratio in contrast to decreased pro-caspase-3 expression in the DLBCL cells. Our findings also demonstrated that 21-kDa Bax was proteolytically cleaved into the 18-kDa Bax in the DLBCL cells exposed to As2S2 at a concentration of 10 µM. As2S2 inhibited proliferation and induced apoptosis of LY1 and LY8 cells in a concentration- and time-dependent manner. The effect was partly due to the induction of mitochondrial-dependent apoptosis involving Bax cleavage.