The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma

Zhong Zhe Lin, Hey Chi Hsu, Chih Hung Hsu, Pei Yen Yeh, Chi Ying F. Huang, Yung Feng Huang, Te Jung Chen, Sung Hsin Kuo, Chiun Hsu, Fu Chang Hu, Yung Ming Jeng, Ying Chung, Ann Lii Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and novel therapies are urgently needed. Recently, aberrant expression of Aurora kinases has been reported in various human cancers including HCC. We sought to investigate the potential of a potent and selective Aurora kinase inhibitor, VE-465, for targeted therapy of HCC. Methods: Cytotoxicity effects of VE-465 were tested in Huh-7 and HepG2 cell lines. Inhibition of Aurora kinase activity was demonstrated by Western blotting and immunofluorescence staining. Mitotic perturbation was visualized by confocal microscopy. Cell cycle profiles and apoptosis were assessed by flow cytometry. In vivo efficacy was determined in nude mice with human HCC xenografts. Results: We demonstrated that VE-465 induced proliferation blockade, histone H3 (Ser10) dephosphorylation, mitotic disturbance, endoreduplication, and apoptosis in Huh-7 and HepG2 cells. We also found that VE-465 suppressed Aurora kinase activity, prevented tumor growth, and induced apoptosis in a Huh-7 xenograft model. Conclusions: These findings show that VE-465 has potent anticancer effects in human HCC. Inhibitors of Aurora kinases may deserve further exploration as molecular targeted agents against HCC.

Original languageEnglish
Pages (from-to)518-527
Number of pages10
JournalJournal of Hepatology
Volume50
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Apoptosis
  • Aurora kinases
  • Hepatocellular carcinoma
  • Small-molecule inhibitor
  • Xenograft

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