Oncotarget

Research Papers:

Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase

Xiaoyu Zeng _, Lin Liu, Mengzhu Zheng, Huimin Sun, Juanjuan Xiao, Tao Lu, Guangqian Huang, Pianpian Chen, Jianmin Zhang, Feng Zhu, Hua Li and Qiuhong Duan

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Oncotarget. 2016; 7:22460-22473. https://doi.org/10.18632/oncotarget.7984

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Abstract

Xiaoyu Zeng1,*, Lin Liu1,*, Mengzhu Zheng2,*, Huimin Sun3, Juanjuan Xiao1, Tao Lu1, Guangqian Huang1, Pianpian Chen4, Jianmin Zhang1, Feng Zhu1, Hua Li2,5, Qiuhong Duan1

1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China

2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China

3Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi, 710032, PR China

4Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China

5School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, PR China

*These authors have contributed equally to this work

Correspondence to:

Feng Zhu, e-mail: fengzhu@hust.edu.cn

Hua Li, e-mail: li_hua@hust.edu.cn

Qiuhong Duan, e-mail: duanqhwz@hust.edu.cn

Keywords: pantoprazole, PPI, TOPK, cell transformation, colon carcinoma

Received: November 11, 2015     Accepted: February 25, 2016     Published: March 8, 2016

ABSTRACT

T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo.


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