2. Academic Validation
  3. Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo

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

  • Oncotarget. 2014 Nov 15;5(21):10342-55. doi: 10.18632/oncotarget.1867.
Shou-Hung Tang 1,  Hsu-Shan Huang 2,  Hong-Ui Wu 3,  Yi-Ta Tsai 4,  Mei-Jen Chuang 1,  Cheng-Ping Yu 5,  Shih-Ming Huang 6,  Guang-Huan Sun 1,  Sun-Yran Chang 7,  Pei-Wen Hsiao 8,  Dah-Shyong Yu 1,  Tai-Lung Cha 9
Affiliations

Affiliations

  • 1 Division of Urology, Department of Surgery, National Defense Medical Center, Taipei, Taiwan, R.O.C.
  • 2 College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, R.O.C.
  • 3 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.
  • 4 Graduate School of Biomedical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.
  • 5 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
  • 6 Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
  • 7 Taipei City Hospital, Taipei, Taiwan, R.O.C.
  • 8 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R.O.C.
  • 9 Division of Urology, Department of Surgery, National Defense Medical Center, Taipei, Taiwan, R.O.C. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C. Graduate School of Biomedical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C. Department of Immunology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
PMID: 25431950 DOI: 10.18632/oncotarget.1867
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 neo-adjuvant 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.

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