Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation

Motoyuki Otsuka, Naoya Kato, Run Xuan Shao, Yujin Hoshida, Hideaki Ijichi, Yukihiro Koike, Hiroyoshi Taniguchi, Masaru Moriyama, Yasushi Shiratori, Takao Kawabe, Masao Omata

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


Hepatocellular carcinoma (HCC) is a common human malignancy. Its high mortality rate is mainly a result of high intrahepatic recurrence and portal venous invasion (PVI). We previously reported that the development of PVI is related to levels of des-gamma-carboxy prothrombin (DCP), a serum protein that increases at a notably higher rate in patients with HCC. Because DCP is produced by a vitamin K shortage, we examined the biological effects of extrinsic supplementation of vitamin K2 in HCC cells in vitro and in vivo. Consequently, vitamin K2 inhibits the growth and invasion of HCC cells through the activation of protein kinase A, which modulates the activities of several transcriptional factors and inhibits the small GTPase Rho, independent of suppression of DCP. In addition, administration of vitamin K 2 to nude mice inoculated with liver tumor cells reduced both tumor growth and body weight loss. In conclusion, similar to an acyclic retinoid-which was previously reported to prevent the recurrence of HCC-vitamin K2, another lipid-soluble vitamin, may be a promising therapeutic means for the management of HCC.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
Issue number1
StatePublished - Jul 2004
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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