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Vitamin K 2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation
Author(s) -
Otsuka Motoyuki,
Kato Naoya,
Shao RunXuan,
Hoshida Yujin,
Ijichi Hideaki,
Koike Yukihiro,
Taniguchi Hiroyoshi,
Moriyama Masaru,
Shiratori Yasushi,
Kawabe Takao,
Omata Masao
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20260
Subject(s) - hepatology , hepatocellular carcinoma , medicine , vitamin , cancer research , in vivo , clinical chemistry , endocrinology , biology , microbiology and biotechnology
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 K(2) in HCC cells in vitro and in vivo. Consequently, vitamin K(2) 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 K(2), another lipid-soluble vitamin, may be a promising therapeutic means for the management of HCC.