We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells.
- Authors
Zhou, Yuanyuan; Chung, Po-yee; Ma, Jessica Yuen-wuen; Lam, Alfred King-yin; Law, Simon; Chan, Kwok-wah; Chan, Albert Sun-chi; Li, Xingshu; Lam, Kim-hung; Chui, Chung-hin; Tang, Johnny Cheuk-on
- 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.
- Subjects
MULTIDRUG resistance; QUINOLINE derivatives; P-glycoprotein; CANCER cells; CANCER chemotherapy; ANTHRACYCLINES; DOXORUBICIN
- Publication
Biology (2079-7737), 2019, Vol 8, Issue 4, p75
- ISSN
2079-7737
- Publication type
Article
- DOI
10.3390/biology8040075