期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2015
卷号：61
期号：4
页码：285-290
DOI：10.3177/jnsv.61.285
出版社：Center for Academic Publications Japan
摘要：Chemoprevention of hepatocellular carcinoma (HCC) is one of the most challenging aspects of medical research. Vitamin K2 (VK2) has been suggested for its chemopreventive role in treatment of HCC, while inconsistent results in clinical trials have been reported. The present study was initiated to add to our insight into the anti-HCC cell proliferative effect of VK2 and its derivatives from a viewpoint of chemical structure. No significant effect was observed with original VK2, while VK2 derivatives bearing both isoprene units and a carboxyl-terminated side chain dose-dependently inhibited the growth of HCC cells without affecting normal liver cells. Loss-of-function analyses revealed that the anti-HCC cell activity by the VK2 derivatives was not mediated by a VK2 binding protein Bcl-2 homologous antagonist/killer (Bak) but rather associated with caspase/transglutaminase-related signaling pathways. Further studies on the carboxylic derivatives of VK2 bearing isoprene structural units introduced in this study might shed new light on the systemic treatment and prevention of HCC.
关键词：vitamin K2;hepatocellular carcinoma;chemoprevention;carboxylic group;isoprene units
