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

doi:10.18632/oncotarget.1867

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 journal › Article › peer-review

29 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 language	English
Pages (from-to)	10342-10355
Number of pages	14
Journal	Oncotarget
Volume	5
Issue number	21
DOIs	https://doi.org/10.18632/oncotarget.1867
Publication status	Published - 2014

Keywords

Ezh2
G2/M cell-cycle arrest
Nsc745885
Proteasome degradation

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.1867

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title = "Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo",

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.",

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

year = "2014",

doi = "10.18632/oncotarget.1867",

language = "English",

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AU - Tang, Shou Hung

AU - Huang, Hsu Shan

AU - Wu, Hong Ui

AU - Tsai, Yi Ta

AU - Chuang, Mei Jen

AU - Yu, Cheng Ping

AU - Huang, Shih Ming

AU - Sun, Guang Huan

AU - Chang, Sun Yran

AU - Hsiao, Pei Wen

AU - Yu, Dah Shyong

AU - Cha, Tai Lung

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Ezh2

KW - G2/M cell-cycle arrest

KW - Nsc745885

KW - Proteasome degradation

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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