Enhancement of anticancer drug sensitivity in multidrug resistance cells overexpressing ATP-binding cassette (ABC) transporter ABCC10 by CP55, a synthetic derivative of 5-cyano-6-phenylpyrimidin.

Autor: Wang JQ; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA., Wang B; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China., Ma LY; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China., Shi Z; Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, PR China., Liu HM; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: liuhm@zzu.edu.cn., Liu Z; Department of Medical Microbiology, Weifang Medical University, Weifang, 261053, PR China. Electronic address: zhijun.liu@wfmc.edu.cn., Chen ZS; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. Electronic address: chenz@stjohns.edu.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2021 Aug 15; Vol. 405 (2), pp. 112728. Date of Electronic Publication: 2021 Jul 08.
DOI: 10.1016/j.yexcr.2021.112728
Abstrakt: ATP-binding cassette (ABC) transporter C10 (ABCC10), also named multidrug resistance protein 7 (MRP7), is a member of ABC transporter superfamily and has been revealed to transport a wide range of chemotherapeutic agents including taxanes, epothilone B, Vinca alkaloids, and anthracyclines. In our previous study, a 5-cyano-6-phenylpyrimidin derivative CP55 was synthesized and found significantly reversal effect of multidrug resistance (MDR) mediated by ABCB1. In this study, we found CP55 also efficiently reversed MDR mediated by ABCC10. Our in vitro study showed that co-treatment with CP55 significantly increased the efficacy of ABCC10-substrate anticancer drugs in MDR cells overexpressing ABCC10. Furthermore, we showed that treatment with CP55 increased the intracellular accumulation of [ 3 H]-labeled anticancer drugs and in-turn decreasing drug efflux by inhibiting the transport activity, without altering ABCC10 protein ex-pression level or cellular localization. Potential CP55-ABCC10 interactions were predicted via docking analysis using human ABCC10 homology model and obtained high docking score. Therefore, CP55 represents a promising therapeutic agent in the combinational treatment of chemo-resistant cancer related to ABCC10.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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