Vitamin K2 Suppresses Proliferation and Motility of Hepatocellular Carcinoma Cells by Activating Steroid and Xenobiotic Receptor

被引：30

作者：

Azuma, Kotaro

Urano, Tomohiko ^{[2
]}

Ouchi, Yasuyoshi

Inoue, Satoshi ^{[1
,2
,3
]}

机构：

[1] Univ Tokyo, Dept Geriatr Med, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan

[2] Univ Tokyo, Dept Antiaging Med, Grad Sch Med, Tokyo 1138655, Japan

[3] Saitama Med Univ, Div Gene Regulat & Signal Transduct, Res Ctr Genom Med, Saitama 3501141, Japan

来源：

ENDOCRINE JOURNAL | 2009年 / 56卷 / 07期

基金：

日本学术振兴会;

关键词：

Vitamin K2; Hepatocellular carcinoma; Steroid and xenobiotic receptor; NUCLEAR RECEPTOR; SXR; MENATETRENONE; BONE; PROTEIN; GROWTH; OSTEOPOROSIS; METABOLISM; FRACTURES; DISEASE;

D O I：

10.1507/endocrj.K09E-108

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Vitamin K2, known as a cofactor for gamma-carboxylase, also serves as a ligand of a nuclear receptor, Steroid and Xenobiotic Receptor (SXR). Several clinical trials revealed that vitamin K2 reduced de novo formation and recurrence of hepatocellular carcinoma (HCC). To examine the role of SXR in HCC as a receptor activated by vitamin K2, the cells stably overexpressing SXR were established using a HCC cell line, HuH7. Overexpression of SXR resulted in reduced proliferation and motility of the cells. Further suppression of proliferation and motility was observed when SXR overexpressing clones were treated with vitamin K2. These results suggest that the activation of SXR could contribute to tumor suppressive effects of vitamin K2 on HCC cells.

引用

收藏

页码：843 / 849

页数：7

相关论文

共 20 条

[1]

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma [J].

Azuma, K ;

Tanaka, M ;

Uekita, T ;

Inoue, S ;

Yokota, J ;

Ouchi, Y ;

Sakai, R .

ONCOGENE, 2005, 24 (30) :4754-4764

[2]

SXR, a novel steroid and xenobiotic-sensing nuclear receptor [J].

Blumberg, B ;

Sabbagh, W ;

Juguilon, H ;

Bolado, J ;

van Meter, CM ;

Ono, ES ;

Evans, RM .

GENES & DEVELOPMENT, 1998, 12 (20) :3195-3205

[3]

Vitamin K and the prevention of fractures - Systematic review and meta-analysis of randomized controlled trials (Publication with Expression of Concern. See vol. 178, pg. 875, 2018) [J].

Cockayne, Sarah ;

Adamson, Joy ;

Lanham-New, Susan ;

Shearer, Martin J. ;

Gilbody, Simon ;

Torgerson, David J. .

ARCHIVES OF INTERNAL MEDICINE, 2006, 166 (12) :1256-1261

[4]

Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver [J].

Habu, D ;

Shiomi, S ;

Tamori, A ;

Takeda, T ;

Tanaka, T ;

Kubo, S ;

Nishiguchi, S .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 292 (03) :358-361

[5]

Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells [J].

Ichikawa, Tomoe ;

Horie-Inoue, Kuniko ;

Ikeda, Kazuhiro ;

Blumberg, Bruce ;

Inoue, Satoshi .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (25) :16927-16934

[6]

Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection [J].

Kakizaki, Satoru ;

Sohara, Naondo ;

Sato, Ken ;

Suzuki, Hideyuki ;

Yanagisawa, Masatoshi ;

Nakajima, Hiroaki ;

Takagi, Hitoshi ;

Naganuma, Atsushi ;

Otsuka, Toshiyuki ;

Takahashi, Hitomi ;

Hamada, Tetsuya ;

Mori, Masatomo .

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2007, 22 (04) :518-522

[7]

Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein [J].

Luo, GB ;

Ducy, P ;

McKee, MD ;

Pinero, GJ ;

Loyer, E ;

Behringer, RR ;

Karsenty, G .

NATURE, 1997, 386 (6620) :78-81

[8]

The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment - A pilot study [J].

Mizuta, T ;

Ozaki, I ;

Eguchi, Y ;

Yasutake, T ;

Kawazoe, S ;

Fujimoto, K ;

Yamamoto, K .

CANCER, 2006, 106 (04) :867-872

[9]

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

Otsuka, M ;

Kato, N ;

Shao, RX ;

Hoshida, Y ;

Ijichi, H ;

Koike, Y ;

Taniguchi, H ;

Moriyama, M ;

Shiratori, Y ;

Kawabe, T ;

Omata, M .

HEPATOLOGY, 2004, 40 (01) :243-251

[10]

Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor κB activation [J].

Ozaki, Iwata ;

Zhang, Hao ;

Mizuta, Toshihiko ;

Ide, Yasushi ;

Eguchi, Yuichiro ;

Yasutake, Tsutomu ;

Sakamaki, Toshiyuki ;

Pestell, Richard G. ;

Yamamoto, Kyosuke .

CLINICAL CANCER RESEARCH, 2007, 13 (07) :2236-2245