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Article: Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to reverse multidrug resistance in cancer cells

TitleDevelopment of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to reverse multidrug resistance in cancer cells
Authors
KeywordsAnticancer
Multidrug resistance
P-glycoprotein
Quinoline compounds
Issue Date2019
PublisherMDPI AG. The Journal's web site is located at https://www.mdpi.com/journal/biology
Citation
Biology, 2019, v. 8 n. 4, article no. 75 How to Cite?
AbstractMultidrug 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.
Persistent Identifierhttp://hdl.handle.net/10722/305455
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 0.815
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, Y-
dc.contributor.authorChung, PY-
dc.contributor.authorMa, JYW-
dc.contributor.authorLam, AKY-
dc.contributor.authorLaw, S-
dc.contributor.authorChan, KW-
dc.contributor.authorChan, ASC-
dc.contributor.authorLi, X-
dc.contributor.authorLam, KH-
dc.contributor.authorChui, CH-
dc.contributor.authorTang, JCO-
dc.date.accessioned2021-10-20T10:09:38Z-
dc.date.available2021-10-20T10:09:38Z-
dc.date.issued2019-
dc.identifier.citationBiology, 2019, v. 8 n. 4, article no. 75-
dc.identifier.issn2079-7737-
dc.identifier.urihttp://hdl.handle.net/10722/305455-
dc.description.abstractMultidrug 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.-
dc.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at https://www.mdpi.com/journal/biology-
dc.relation.ispartofBiology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAnticancer-
dc.subjectMultidrug resistance-
dc.subjectP-glycoprotein-
dc.subjectQuinoline compounds-
dc.titleDevelopment of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to reverse multidrug resistance in cancer cells-
dc.typeArticle-
dc.identifier.emailLaw, S: slaw@hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.authorityLaw, S=rp00437-
dc.identifier.authorityChan, KW=rp00330-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/biology8040075-
dc.identifier.pmid31581572-
dc.identifier.pmcidPMC6955663-
dc.identifier.scopuseid_2-s2.0-85073560105-
dc.identifier.hkuros328111-
dc.identifier.volume8-
dc.identifier.issue4-
dc.identifier.spagearticle no. 75-
dc.identifier.epagearticle no. 75-
dc.identifier.isiWOS:000505517600016-
dc.publisher.placeSwitzerland-

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