XZH-5 inhibits STAT3 phosphorylation and causes apoptosis in human hepatocellular carcinoma cells

被引:0
作者
Yan Liu
Aiguo Liu
Zhenghu Xu
Wenying Yu
Hong Wang
Chenglong Li
Jiayuh Lin
机构
[1] College of Medicine,Center for Childhood Cancer, Department of Pediatrics
[2] The Ohio State University,Department of Chemistry and Biochemistry
[3] Miami University,Division of Medicinal Chemistry and Pharmacognosy
[4] College of Pharmacy,Department of Pediatrics
[5] The Ohio State University,Department of Cancer Biology
[6] Tongji Hospital,undefined
[7] Huazhong University of Science and Technology,undefined
[8] Vanderbilt University Medical Center,undefined
来源
Apoptosis | 2011年 / 16卷
关键词
Interleukin-6; STAT3; Hepatocellular carcinoma; Apoptosis;
D O I
暂无
中图分类号
学科分类号
摘要
Growing evidence has demonstrated that signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in patients with hepatocellular carcinoma (HCC), plays an important role in HCC development, progression, and prognosis. Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine, which may induce STAT3 activation in a variety of human cancers. In this study, we demonstrated that blocking STAT3 phosphorylation with STAT3 small molecule inhibitors SD-1029 and Stattic caused apoptosis in HCC cells. Then we characterized the inhibitory effects of a novel small molecule XZH-5 on STAT3 phosphorylation in HCC cell lines. XZH-5 reduced constitutive STAT3 phosphorylation at Tyr705 and the expression of STAT3 downstream genes. The inhibition of STAT3 in HCC cells resulted in the induction of apoptosis and reduction of colony forming ability. In addition, XZH-5 also inhibited IL-6-induced STAT3 phosphorylation, nuclear translocation and STAT3 DNA binding activity. In contrast, it had no effect on IFN-γ-induced STAT1 phosphorylation, indicating the more selective effects on STAT3. These results suggested that XZH-5 may serve as a lead compound for further development of STAT3 specific small molecule inhibitors for HCC therapy.
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页码:502 / 510
页数:8
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