کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2525301 | 1119606 | 2009 | 9 صفحه PDF | دانلود رایگان |

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 caner cell lines was shown to be susceptible to selenocystine, with IC50 values ranging from 3.6 to 37.0 μM. 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.
Journal: Biomedicine & Pharmacotherapy - Volume 63, Issue 2, February 2009, Pages 105–113