title: Carboxylic Derivatives of Vitamin K2 Inhibit Hepatocellular Carcinoma Cell Growth through Caspase/Transglutaminase-Related Signaling Pathways.
abstract: 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.
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies.
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujii
authors.forename: Akitaka
authors.initials: A
authors.lastname: Shimizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
mesh_terms: D002264:Carboxylic Acids / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D011503:Transglutaminases / Q000378:metabolism; D024482:Vitamin K 2 / Q000031:analogs & derivatives*
chemical_list: D002264:Carboxylic Acids; D024482:Vitamin K 2; D011503:Transglutaminases; D020169:Caspases