Selenocystine induces reactive oxygen species-mediated apoptosis in human cancer cells.

Abstract

Epidemiological and clinical studies have demonstrated that dietary supplementation of selenium (Se) could reduce the incidence of human cancers. In this study, selenocystine, a nutritionally available selenoamino acid, was identified as a novel agent with broad-spectrum antitumor activity. A panel of eight human cancer cell lines was shown to be susceptible to selenocystine, with IC(50) values ranging from 3.6 to 37.0 microM. Selenocystine induced dose-dependent apoptosis in A375, HepG2 and MCF7 cells was evaluated by flow cytometric analysis and annexin-V staining assay. Mechanistic studies showed time- and dose-dependent increases in intracellular reactive oxygen species (ROS) in susceptible cancer cells (MCF7 and HepG2 cells) treated with selenocystine. However, selenocystine-induced ROS overproduction was not observed in non-susceptible normal human fibroblast Hs68 cells. Significant DNA strand breaks were observed in selenocystine-treated MCF7 and HepG2 cells as examined by single-cell gel electrophoresis (Comet assay). The thiol-reducing antioxidants, glutathione and N-acetylcysteine, inhibited intracellular ROS generation, DNA strand breaks and accumulation of sub-G1 population in MCF7 cells exposed to selenocystine. Our results suggest a possible role of ROS as a mediator of the signaling pathway of selenocystine-induced, DNA damage-mediated apoptosis in susceptible cancer cells.

• Authors: Tianfeng Chen, Yum-Shing Wong
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 63 Issue 2 Pg. 105-13 (Feb 2009) ISSN: 1950-6007 [Electronic] France
• PMID: 18511231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antineoplastic Agents
• Organoselenium Compounds
• Reactive Oxygen Species
• selenocystine
• Cystine

Topics

• Annexin A5 (metabolism)
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Comet Assay
• Cystine (administration & dosage, analogs & derivatives, pharmacology)
• DNA Breaks (drug effects)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Inhibitory Concentration 50
• Organoselenium Compounds (administration & dosage, pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Time Factors