RRC ID |
42189
|
著者 |
Otsuka M, Kato N, Shao RX, Hoshida Y, Ijichi H, Koike Y, Taniguchi H, Moriyama M, Shiratori Y, Kawabe T, Omata M.
|
タイトル |
Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation.
|
ジャーナル |
Hepatology
|
Abstract |
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.
|
巻・号 |
40(1)
|
ページ |
243-51
|
公開日 |
2004-7-1
|
DOI |
10.1002/hep.20260
|
PMID |
15239108
|
MeSH |
Animals
Carcinoma, Hepatocellular / enzymology*
Carcinoma, Hepatocellular / pathology*
Cell Division / drug effects
Cell Line, Tumor
Cyclic AMP-Dependent Protein Kinases / metabolism*
Enzyme Activation
Humans
Liver Neoplasms / enzymology*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Liver Neoplasms / physiopathology
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasm Invasiveness
Neoplasm Transplantation
Signal Transduction / drug effects
Vitamin K 2 / pharmacology*
cdc25 Phosphatases / metabolism
rhoA GTP-Binding Protein / antagonists & inhibitors
|
IF |
14.679
|
引用数 |
99
|
WOS 分野
|
GASTROENTEROLOGY & HEPATOLOGY
|
リソース情報 |
ヒト・動物細胞 |
HepG2
NIH3T3 |