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新型组蛋白去乙酰化酶抑制剂SK-7041可诱导胰腺癌细胞系发生G2-M期细胞周期阻滞并引发凋亡。

SK-7041, a new histone deacetylase inhibitor, induces G2-M cell cycle arrest and apoptosis in pancreatic cancer cell lines.

作者信息

Ryu Ji Kon, Lee Woo Jin, Lee Kwang Hyuck, Hwang Jin-Hyeok, Kim Yong-Tae, Yoon Yong Bum, Kim Chung Yong

机构信息

Departments of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul 110-744, South Korea.

出版信息

Cancer Lett. 2006 Jun 8;237(1):143-54. doi: 10.1016/j.canlet.2005.05.040. Epub 2005 Jul 11.

DOI:10.1016/j.canlet.2005.05.040
PMID:16009488
Abstract

A novel hybrid synthetic histone deacetylase inhibitor, SK-7041, was synthesized from hydroaxamic acid of trichostatin A (TSA) and pyridyl ring of MS-275. TSA and SK-7041 both induced apoptosis and G2-M cell cycle arrest in pancreatic cancer cell lines. The expressions of p21 and cyclin D2 were up-regulated and that of cyclin B1 was down-regulated by TSA or SK-7041. The expression levels of Mcl-1 and Bcl-XL but not those of Bcl-2, Bax, and Bak were suppressed by TSA or SK-7041 treatment. SK-7041 or TSA induced apoptosis and G2-M cell cycle arrest by up-regulating p21 and down-regulating cyclin B1, Mcl-1, and Bcl-XL.

摘要

一种新型杂合合成组蛋白去乙酰化酶抑制剂SK-7041，由曲古抑菌素A（TSA）的羟肟酸和MS-275的吡啶环合成。TSA和SK-7041均能诱导胰腺癌细胞系凋亡并使细胞周期阻滞于G2-M期。TSA或SK-7041可上调p21和细胞周期蛋白D2的表达，下调细胞周期蛋白B1的表达。TSA或SK-7041处理可抑制Mcl-1和Bcl-XL的表达水平，但不影响Bcl-2、Bax和Bak的表达水平。SK-

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