Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo

Shou Hung Tang, Hsu Shan Huang, Hong Ui Wu, Yi Ta Tsai, Mei Jen Chuang, Cheng Ping Yu, Shih Ming Huang, Guang Huan Sun, Sun Yran Chang, Pei Wen Hsiao, Dah Shyong Yu, Tai Lung Cha

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The polycomb group gene, EZH2, is highly expressed in advanced bladder cancer. Here we demonstrated that down-regulation of EZH2 in tumor tissues after neoadjuvant chemotherapy correlated with good therapeutic response in advanced bladder cancer. We next developed a small molecule, NSC745885, derived from natural anthraquinone emodin, which down-regulated EZH2 via proteasome-mediated degradation. NSC745885 showed potent selective toxicity against multiple cancer cell lines but not normal cells. NSC745885 treatment overcame multiple-drug resistance and inhibited growth of resistant cancer cells. Over-expression of EZH2 in cancer cells attenuated effects of NSC745885, suggesting that down-regulation of EZH2 was responsible for growth inhibition of NSC745885. NSC745885 also suppressed tumor growth and down-regulated EZH2 in vivo. These results indicate that NSC7455889 suppresses bladder cancer by targeting EZH2.

Original languageEnglish
Pages (from-to)10342-10355
Number of pages14
JournalOncotarget
Volume5
Issue number21
Publication statusPublished - 2014

Keywords

  • Ezh2
  • G2/M cell-cycle arrest
  • Nsc745885
  • Proteasome degradation

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Tang, S. H., Huang, H. S., Wu, H. U., Tsai, Y. T., Chuang, M. J., Yu, C. P., Huang, S. M., Sun, G. H., Chang, S. Y., Hsiao, P. W., Yu, D. S., & Cha, T. L. (2014). Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo. Oncotarget, 5(21), 10342-10355.