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

Abstract

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.

• Authors: Tianfeng Chen, Wenjie Zheng, Yum-Shing Wong, Fang Yang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 62 Issue 2 Pg. 77-84 (Feb 2008) ISSN: 0753-3322 [Print] France
• PMID: 18222058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,2,5-selenadiazolo-(3,4-d)pyrimidine-5,7-(4H,6H)-dione
• Antineoplastic Agents
• Proto-Oncogene Proteins c-bcl-2
• Pyrimidinones
• Reactive Oxygen Species
• Caspase 8
• Caspase 9

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy)
• Caspase 8 (drug effects, metabolism)
• Caspase 9 (drug effects, metabolism)
• Cell Line, Tumor
• DNA Fragmentation (drug effects)
• Female
• G1 Phase (drug effects)
• Gene Expression Regulation (drug effects)
• Humans
• Liver Neoplasms (drug therapy)
• Melanoma (drug therapy)
• Mitochondria (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (drug effects, genetics)
• Pyrimidinones (pharmacology)
• Reactive Oxygen Species (metabolism)