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.
Chen
Tianfeng
T
Department of Biology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Zheng
Wenjie
W
Wong
Yum-Shing
YS
Yang
Fang
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D011744:Pyrimidinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
C529179:1,2,5-selenadiazolo-(3,4-d)pyrimidine-5,7-(4H,6H)-dione; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011744:Pyrimidinones; D017382:Reactive Oxygen Species; D053181:Caspase 8; D053453:Caspase 9