Mitochondria-mediated apoptosis in human breast carcinoma MCF-7 cells induced by a novel selenadiazole derivative

The role of organoselenium compounds as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical and clinical studies. In this study, a novel selenadiazole derivative, 1, 2,5 -selenadiazolo-[3,4-d] pyrimidine-5,7-(4H,6H)-dione (SPO), is identified as a potent antiproliferative agent against human breast adrenocarcinoma MCF-7 cells, human hepatoma HepG2 cells and human melanoma A375 cells. Induction of apoptosis in MCF-7 and A375 cells by SPO was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms found that SPO treatments induced activation of caspase-8 and caspase-9, overproduction of reactive oxygen species, and depletion of mitochondrial membrane potential (Delta Psi m) through regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Our findings suggest that SPO is a promising novel organoselenium compound with potential in the treatment of human cancers. (c) 2007 Elsevier Masson SAS. All rights reserved.