Mimic of manganese superoxide dismutase induces apoptosis in human acute myeloid leukemia cells

Abstract

Increasing manganese superoxide dismutase (MnSOD) expression can suppress the malignant phenotype in various cancer cell lines and suppress tumor formation in xenograft and transgenic mouse models. A mimic of manganese superoxide dismutase (MnSODm), synthesized by a chemical method, has been shown to possess antitumor properties. However, the anticancer activity of MnSODm in acute myeloid leukemia (AML) is still obscure. In this study, we investigated the effects of MnSODm on the apoptosis of human leukemia HL-60 cells. Results showed that MnSODm significantly reduced the proliferation of HL-60 cells in a concentration- and time-dependent manner. By flow cytometric analysis, we found that MnSODm treatment resulted in increased apoptosis in HL-60 cells. Further analysis demonstrated involvement of activation of the caspase cascade, cleavage of poly(ADP-ribose) polymerase (PARP) and release of cytochrome c in MnSODm-induced apoptosis. The results also showed that the expression of anti-apoptotic Bcl-2 and Bid were dose-dependently decreased, whereas the expression of pro-apoptotic Bax protein was increased. Thus, MnSODm induced apoptosis in HL-60 cells via mitochondria-mediated, caspase-dependent pathways. MnSODm inhibition of Akt phosphorylation may contribute to MnSODm-mediated acute myeloid leukemia cell growth inhibition and apoptosis induction.