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Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase.
Oncotarget 2016; 7(16):22460-73O

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+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.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.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26967058

Citation

Zeng, Xiaoyu, et al. "Pantoprazole, an FDA-approved Proton-pump Inhibitor, Suppresses Colorectal Cancer Growth By Targeting T-cell-originated Protein Kinase." Oncotarget, vol. 7, no. 16, 2016, pp. 22460-73.
Zeng X, Liu L, Zheng M, et al. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2016;7(16):22460-73.
Zeng, X., Liu, L., Zheng, M., Sun, H., Xiao, J., Lu, T., ... Duan, Q. (2016). Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget, 7(16), pp. 22460-73. doi:10.18632/oncotarget.7984.
Zeng X, et al. Pantoprazole, an FDA-approved Proton-pump Inhibitor, Suppresses Colorectal Cancer Growth By Targeting T-cell-originated Protein Kinase. Oncotarget. 2016 Apr 19;7(16):22460-73. PubMed PMID: 26967058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. AU - Zeng,Xiaoyu, AU - Liu,Lin, AU - Zheng,Mengzhu, AU - Sun,Huimin, AU - Xiao,Juanjuan, AU - Lu,Tao, AU - Huang,Guangqian, AU - Chen,Pianpian, AU - Zhang,Jianmin, AU - Zhu,Feng, AU - Li,Hua, AU - Duan,Qiuhong, PY - 2015/11/11/received PY - 2016/02/25/accepted PY - 2016/3/12/entrez PY - 2016/3/12/pubmed PY - 2017/12/5/medline KW - PPI KW - TOPK KW - cell transformation KW - colon carcinoma KW - pantoprazole SP - 22460 EP - 73 JF - Oncotarget JO - Oncotarget VL - 7 IS - 16 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26967058/Pantoprazole_an_FDA_approved_proton_pump_inhibitor_suppresses_colorectal_cancer_growth_by_targeting_T_cell_originated_protein_kinase_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=7984 DB - PRIME DP - Unbound Medicine ER -