title: Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Mengzhu
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Guangqian
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Pianpian
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.|School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Duan
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D062105:Molecular Docking Simulation; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000970:Antineoplastic Agents; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase
keywords: PPI; TOPK; cell transformation; colon carcinoma; pantoprazole