Oncotarget

Research Papers:

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 and Tai-Lung Cha _

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Oncotarget. 2014; 5:10342-10355. https://doi.org/10.18632/oncotarget.1867

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Abstract

Shou-Hung Tang1, Hsu-Shan Huang2, Hong-Ui Wu3, Yi-Ta Tsai4, Mei-Jen Chuang1, Cheng-Ping Yu5, Shih-Ming Huang6, Guang-Huan Sun1, Sun-Yran Chang7, Pei-Wen Hsiao8, Dah-Shyong Yu1 and Tai-Lung Cha1,3,4,6,9

1 Division of Urology, Department of Surgery, Tri-Service General Hospital, 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 Department of Immunology, National Defense Medical Center, Taipei, Taiwan, R.O.C.

Correspondence:

Tai-Lung Cha, email:

Keywords: EZH2, NSC745885, proteasome degradation, G2/M cell-cycle arrest

Received: January 20, 2014 Accepted: March 24, 2014 Published: March 26, 2014

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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