Development of a novel quinoline derivative as a P-glycoprotein inhibitor to reverse multidrug resistance in cancer cells

Loading...
Thumbnail Image
File version
Version of Record (VoR)
Author(s)
Zhou, Y
Chung, PY
Ma, JYW
Lam, AKY
Law, S
Chan, KW
Chan, ASC
Li, X
Lam, KH
Chui, CH
Tang, JCO
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2019
Size
File type(s)
Location
License
http://creativecommons.org/licenses/by/4.0/
Abstract

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.

Journal Title
Biology
Conference Title
Book Title
Edition
Volume
8
Issue
4
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Item Access Status
Note
Access the data
Related item(s)
Subject
Biological sciences
Biochemistry and cell biology
anticancer
multidrug resistance
p-glycoprotein
quinoline compounds
Persistent link to this record
Citation
Zhou, Y; Chung, PY; Ma, JYW; Lam, AKY; Law, S; Chan, KW; Chan, ASC; Li, X; Lam, KH; Chui, CH; Tang, JCO, Development of a novel quinoline derivative as a P-glycoprotein inhibitor to reverse multidrug resistance in cancer cells, Biology, 2019, 8 (4), pp. 75:1-75:19
Collections