, Volume 16, Issue 5, pp 502–510 | Cite as

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

  • Yan Liu
  • Aiguo Liu
  • Zhenghu Xu
  • Wenying Yu
  • Hong Wang
  • Chenglong Li
  • Jiayuh Lin
Original Paper


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.


Interleukin-6 STAT3 Hepatocellular carcinoma Apoptosis 

Supplementary material

10495_2011_578_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yan Liu
    • 1
    • 5
  • Aiguo Liu
    • 1
    • 4
  • Zhenghu Xu
    • 2
  • Wenying Yu
    • 3
  • Hong Wang
    • 2
  • Chenglong Li
    • 3
  • Jiayuh Lin
    • 1
  1. 1.Center for Childhood Cancer, Department of PediatricsCollege of Medicine, The Ohio State UniversityColumbusUSA
  2. 2.Department of Chemistry and BiochemistryMiami UniversityOxfordUSA
  3. 3.Division of Medicinal Chemistry and PharmacognosyCollege of Pharmacy, The Ohio State UniversityColumbusUSA
  4. 4.Department of PediatricsTongji Hospital, Huazhong University of Science and TechnologyWuhanPeople’s Republic of China
  5. 5.Department of Cancer BiologyVanderbilt University Medical CenterNashvilleUSA

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