Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
| Autor: | Yuanyuan Zhou, Xingshu Li, Simon Law, Chung-Hin Chui, Albert S. C. Chan, Jessica Yuen Wuen Ma, Johnny Cheuk On Tang, Kwok Wah Chan, Alfred King-Yin Lam, Kim Hung Lam, Po-yee Chung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
P-glycoprotein Inhibitor
General Immunology and Microbiology quinoline compounds Biology anticancer General Biochemistry Genetics and Molecular Biology Article Multiple drug resistance lcsh:Biology (General) multidrug resistance p-glycoprotein Cancer cell medicine Cancer research biology.protein Doxorubicin Efflux General Agricultural and Biological Sciences Cytotoxicity lcsh:QH301-705.5 Intracellular medicine.drug P-glycoprotein |
| Zdroj: | Biology Volume 8 Issue 4 Biology, Vol 8, Iss 4, p 75 (2019) |
| ISSN: | 2079-7737 |
| DOI: | 10.3390/biology8040075 |
| Popis: | Multidrug resistance (MDR) is one of conventional cancer chemotherapy&rsquo 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&rsquo s MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a&rsquo 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&rsquo 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. |
| Databáze: | OpenAIRE |
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