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Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase.
Oncotarget 2017; 8(24):39143-39153O

Abstract

T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole. Results of an in vivo study demonstrated that gavage of ilaprazole in HCT116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after ilaprazole treatment. Our results suggested that ilaprazole inhibited the cancer growth by targeting TOPK both in vitro and in vivo.

Authors+Show Affiliations

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Livzon Pharmaceutical Group Inc., Zhuhai 519090, China.School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28388576

Citation

Zheng, Mengzhu, et al. "Proton Pump Inhibitor Ilaprazole Suppresses Cancer Growth By Targeting T-cell-originated Protein Kinase." Oncotarget, vol. 8, no. 24, 2017, pp. 39143-39153.
Zheng M, Luan S, Gao S, et al. Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2017;8(24):39143-39153.
Zheng, M., Luan, S., Gao, S., Cheng, L., Hao, B., Li, J., ... Li, H. (2017). Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. Oncotarget, 8(24), pp. 39143-39153. doi:10.18632/oncotarget.16609.
Zheng M, et al. Proton Pump Inhibitor Ilaprazole Suppresses Cancer Growth By Targeting T-cell-originated Protein Kinase. Oncotarget. 2017 Jun 13;8(24):39143-39153. PubMed PMID: 28388576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. AU - Zheng,Mengzhu, AU - Luan,Shanshan, AU - Gao,Suyu, AU - Cheng,Li, AU - Hao,Bin, AU - Li,Jiacheng, AU - Chen,Yao, AU - Hou,Xuemei, AU - Chen,Lixia, AU - Li,Hua, PY - 2017/01/23/received PY - 2017/03/02/accepted PY - 2017/4/8/pubmed PY - 2018/6/8/medline PY - 2017/4/8/entrez KW - Ilaprazole KW - PPI KW - TOPK inhibitor KW - cancer KW - drug repurposing SP - 39143 EP - 39153 JF - Oncotarget JO - Oncotarget VL - 8 IS - 24 N2 - T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole. Results of an in vivo study demonstrated that gavage of ilaprazole in HCT116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after ilaprazole treatment. Our results suggested that ilaprazole inhibited the cancer growth by targeting TOPK both in vitro and in vivo. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28388576/Proton_pump_inhibitor_ilaprazole_suppresses_cancer_growth_by_targeting_T_cell_originated_protein_kinase_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=16609 DB - PRIME DP - Unbound Medicine ER -