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标题：Gomisin A Enhances Tumor Necrosis Factor-α-Induced G1 Cell Cycle Arrest via Signal Transducer and Activator of Transcription 1-Mediated Phosphorylation of Retinoblastoma Protein
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作者：Pornthip Waiwut ; Myoung-Sook Shin ; Satoru Yokoyama 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：2012
卷号：35
期号：11
页码：1997-2003
DOI：10.1248/bpb.b12-00450
出版社：The Pharmaceutical Society of Japan
摘要：Gomisin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra chinensis , has been reported as an anti-cancer substance. In this study, we investigated the effects of gomisin A on cancer cell proliferation and cell cycle arrest in HeLa cells. Gomisin A significantly inhibited cell proliferation in a dose-dependent manner after 72 h treatment, especially in the presence of tumor necrosis factor-α (TNF-α), due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation. In addition, gomisin A in combination with TNF-α strongly suppressed the expression of signal transducer and activator of transcription 1 (STAT1). Inhibition of STAT1 pathways by a small-interfering RNA against STAT1 and AG490 Janus kinase (JAK) kinase inhibitor AG490 reduced the cyclin D1 expression and RB phosphorylation, indicating that JAK-mediated STAT1 activation is involved in gomisin A-induced G1 cell cycle arrest.
关键词：gomisin A;tumor necrosis factor-α;cell cycle;cyclin D1;Retinoblastoma