Selenocystine induces reactive oxygen species-mediated apoptosis in human cancer cells.
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.
Chen
Tianfeng
T
Department of Biology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Wong
Yum-Shing
YS
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D020552:Comet Assay; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D053960:DNA Breaks / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D017304:Annexin A5; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C009226:selenocystine; D003553:Cystine