1,4-Diselenophene-1,4-diketone Triggers Caspase-Dependent Apoptosis in Human Melanoma.A375 Cells through Induction of Mitochondrial Dysfunction
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摘要Epidemiological, preclinical and clinical studies have supported the role of selenocompounds as potential cancer chemopreventive and chemotherapeutic agents. In this study, a novel selenophene-based compound, 1,4-diselenophene-1,4-diketone (DSeD), has been synthesized by Double Friedel Crafts reaction and identified as a potent antiproliferative agent against a panel of six human caner cell lines. Despite this potency, DSeD was relatively nontoxic toward human normal cells, HS68 fibroblasts and HK-2 kidney cells. These results suggest that DSeD possesses great selectivity between cancer and normal cells. Induction of apoptosis in human melanoma A375 cells by DSeD was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Activation of caspase-9 and depletion of mitochondrial membrane potential indicated the initiation of the mitochondria-mediated apoptosis pathway. Pretreatment of cells with general caspase inhibitor z-VAD-fmk and caspase-9 inhibitor z-LEHD-fmk significantly suppressed the cell apoptosis, demonstrating the important roles of caspase and mitochondria in DSeD-induced apoptotic cell death. Furthermore, DSeD-induced apoptosis was found independent of reactive oxygen species generation. Taken together, our results suggest that DSeD induces caspase-dependent apoptosis in A375 cells through activation of mitochondria-mediated apoptosis pathway.
著者Luo Y, Li XL, Huang XC, Wong YS, Chen TF, Zhang YB, Zheng WJ
期刊名稱Chemical and Pharmaceutical Bulletin
出版年份2011
月份10
日期1
卷號59
期次10
出版社PHARMACEUTICAL SOC JAPAN
頁次1227 - 1232
國際標準期刊號0009-2363
語言英式英語
關鍵詞apoptosis; caspase activation; mitochondria; reactive oxygen species; selenium
Web of Science 學科類別Chemistry; Chemistry, Medicinal; CHEMISTRY, MEDICINAL; Chemistry, Multidisciplinary; CHEMISTRY, MULTIDISCIPLINARY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

上次更新時間 2021-23-01 於 01:01