文章基本信息

标题：Silibinin Prevents UV-Induced HaCaT Cell Apoptosis Partly through Inhibition of Caspase-8 Pathway
本地全文：下载
作者：Lin-Hao Li ; Li-Jun Wu ; Shin-ichi Tashiro 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：6
页码：1096-1101
DOI：10.1248/bpb.29.1096
出版社：The Pharmaceutical Society of Japan
摘要：Silymarin is a polyphenolic flavonoid from milk thistle ( Silybum marianum ), which has anti-inflammatory, cytoprotective, and anticarcinogenic effects.¹⁾ In this study, we assessed the effect of silibinin (Fig. 1), the major active compound in silymarin, on ultraviolet light (UV)-induced cell apoptosis in HaCaT cells, a human keratinocyte cell line. Pretreatment with silibinin 500 μ M significantly inhibited UV-induced apoptosis in HaCaT cells after 9 h incubation. The expression of Fas-associating protein with death domain (FADD), a downstream molecule of the death receptor pathway, was completely eliminated by silibinin treatment in UV-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8, whose activation induced cell apoptosis²⁾ and decreased the release of cytochrome c from mitochondria. The caspase-8 inhibitor z-IETD-fmk at 10 μ M increased the ratio of UV-irradiated HaCaT cell viability, suggesting that UV-induced HaCaT cell apoptosis was partially due to activation of the caspase-8 pathway. Moreover, UV-induced cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP), were also reduced by silibinin pretreatment. While unexpectedly, it was found in our study that pretreatment with silibinin increased HaCaT cell death by CD95 agonistic antibody CH11. Consequently, the protective effect of silibinin against UV irradiation in HaCaT cells is exerted by inactivation of caspase-8 after direct down-regulation of FADD expression, resulting in blockage of UV-induced apoptosis.
关键词：silibinin;anti-apoptosis;HaCaT cell;UV irradiation;Fas-associating protein with death domain (FADD);caspase