SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G₀/G₁ phase arrest and apoptosis in human hepatic carcinoma cells

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• 作者：Yuanyuan Han^a ; ¹ ; Haiyun He^a ; ¹ ; Feng Peng^b ; ¹ ; Jiyan Liu^a ; Xiaoyun Dai^a ; Hongjun Lin^a ; Youzhi Xu^a ; Tian Zhou^a ; Yongqiu Mao^a ; Gang Xie^a ; Shengyong Yang^a ; Luoting Yu^a ; Li Yang^a ; ; Yinglan Zhao^a ; ^{alancenxb@sina.com}
• 关键词：SKLB70326 ; Hepatocellular carcinoma ; G0/G1 arrest ; Cyclin-dependent kinase ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：18 May, 2012
• 卷：421
• 期：4
• 页码：684-689
• 文件大小：920 K

摘要

We previously reported the potential of a novel small molecule 3-amino-6-(3-methoxyphenyl)thieno[2.3-b]pyridine-2-carboxamide (SKLB70326) as an anticancer agent. In the present study, we investigated the anticancer effects and possible mechanisms of SKLB70326 in vitro. We found that SKLB70326 treatment significantly inhibited human hepatic carcinoma cell proliferation in vitro, and the HepG2 cell line was the most sensitive to its treatment. The inhibition of cell proliferation correlated with G₀/G₁ phase arrest, which was followed by apoptotic cell death. The SKLB70326-mediated cell-cycle arrest was associated with the downregulation of cyclin-dependent kinase (CDK) 2, CDK4 and CDK6 but not cyclin D1 or cyclin E. The phosphorylation of the retinoblastoma protein (Rb) was also observed. SKLB70326 treatment induced apoptotic cell death via the activation of PARP, caspase-3, caspase-9 and Bax as well as the downregulation of Bcl-2. The expression levels of p53 and p21 were also induced by SKLB70326 treatment. Moreover, SKLB70326 treatment was well tolerated. In conclusion, SKLB70326, a novel cell-cycle inhibitor, notably inhibits HepG2 cell proliferation through the induction of G₀/G₁ phase arrest and subsequent apoptosis. Its potential as a candidate anticancer agent warrants further investigation.