Silibinin Prevents UV-Induced HaCaT Cell Apoptosis Partly through Inhibition of Caspase-8 Pathway(Pharmacology)

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概要

• 論文の詳細を見る

• Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective, and anticarcinogenic effects. 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 500μM significantly inhibited UV-induced apoptosis in HaCaT cells after 9h 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 apoptosis and decreased the release of cytochrome c from mitochondria. The caspase-8 inhibitor z-IETD-fmk at 10μM 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.

• 社団法人日本薬学会の論文
• 2006-06-01

著者

• Tashiro Shin-ichi

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• TASHIRO Shin-ichi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• ONODERA Satoshi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• IKEJIMA Takashi

  China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical Unive

• Wu Li-jun

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Wu L

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Onodera S

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• Onodera Satoshi

  昭和薬科大学 病態科

• Ikejima Takashi

  China-japan Res. Inst. Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univ. Chn

• LI Lin-Hao

  China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical Unive

• UCHIUMI Fumiaki

  Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Tashiro Shin-ichi

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera Satoshi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Tashiro Shin-ichi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Li Lin-hao

  China-japan Research Institute Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univer

• Uchiumi Fumiaki

  Department Of Gene Regulation Faculty Of Pharmaceutical Sciences Tokyo University Of Science

• Uchiumi Fumiaki

  Department Of Biochemistry Faculty Of Pharmaceutical Sciences Tokyo University Of Science

• Tashiro S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Ikejima Takashi

  China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University

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