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Open AccessArticle

Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells

1
State Key Laboratory of Chemical Biology and Drug Discovery, Lo Ka Chung Centre for Natural Anticancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong 999077, China
2
School of Optometry, The Hong Kong Polytechnic University, Hong Kong 999077, China
3
Griffith Medical School, Griffith University, Gold Coast, QLD 4222, Australia
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Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
5
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
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School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
*
Authors to whom correspondence should be addressed.
Biology 2019, 8(4), 75; https://doi.org/10.3390/biology8040075
Received: 6 September 2019 / Revised: 26 September 2019 / Accepted: 27 September 2019 / Published: 1 October 2019
(This article belongs to the Section Cell Biology)
Multidrug resistance (MDR) is one of conventional cancer chemotherapy’s limitations. Our group previously synthesized a series of quinoline-based compounds in an attempt to identify novel anticancer agents. With a molecular docking analysis, the novel compound 160a was predicted to target p-glycoprotein, an MDR candidate. The purpose of this study is to evaluate 160a’s MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a’s inhibitory effect, we used a series of parental cancer cell lines (A549, LCC6, KYSE150, and MCF-7), the corresponding doxorubicin-resistant cell lines, an MTS cytotoxicity assay, an intracellular doxorubicin accumulation test, and multidrug resistance assays. The Compusyn program confirmed, with a combination index (CI) value greater than 1, that 160a combined with doxorubicin exerts a synergistic effect. Intracellular doxorubicin accumulation and transported calcein acetoxymethyl (AM) (a substrate for p-glycoprotein) were both increased when cancer cells with MDR were treated with compound 160a. We also showed that compound 160a’s MDR reversal effect can persist for at least 1 h. Taken together, these results suggest that the quinoline compound 160a possesses high potential to reverse MDR by inhibiting p-glycoprotein-mediated drug efflux in cancer cells with MDR. View Full-Text
Keywords: anticancer; multidrug resistance; p-glycoprotein; quinoline compounds anticancer; multidrug resistance; p-glycoprotein; quinoline compounds
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Zhou, Y.; Chung, P.-Y.; Ma, J. .-W.; Lam, A. .-Y.; Law, S.; Chan, K.-W.; Chan, A. .-C.; Li, X.; Lam, K.-H.; Chui, C.-H.; Tang, J. .-O. Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells. Biology 2019, 8, 75.

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