Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
Identifieur interne : 000891 ( Main/Exploration ); précédent : 000890; suivant : 000892Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
Auteurs : Yuanyuan Zhou ; Po-Yee Chung ; Jessica Yuen-Wuen Ma ; Alfred King-Yin Lam ; Simon Law ; Kwok-Wah Chan ; Albert Sun-Chi Chan ; Xingshu Li ; Kim-Hung Lam ; Chung-Hin Chui ; Johnny Cheuk-On TangSource :
- Biology [ 2079-7737 ] ; 2019.
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.
Url:
DOI: 10.3390/biology8040075
PubMed: 31581572
PubMed Central: 6955663
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells</title><author><name sortKey="Zhou, Yuanyuan" sort="Zhou, Yuanyuan" uniqKey="Zhou Y" first="Yuanyuan" last="Zhou">Yuanyuan Zhou</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Chung, Po Yee" sort="Chung, Po Yee" uniqKey="Chung P" first="Po-Yee" last="Chung">Po-Yee Chung</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Ma, Jessica Yuen Wuen" sort="Ma, Jessica Yuen Wuen" uniqKey="Ma J" first="Jessica Yuen-Wuen" last="Ma">Jessica Yuen-Wuen Ma</name><affiliation><nlm:aff id="af2-biology-08-00075">School of Optometry, The Hong Kong Polytechnic University, Hong Kong 999077, China;<email>majessicayuenwuen@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Lam, Alfred King Yin" sort="Lam, Alfred King Yin" uniqKey="Lam A" first="Alfred King-Yin" last="Lam">Alfred King-Yin Lam</name><affiliation><nlm:aff id="af3-biology-08-00075">Griffith Medical School, Griffith University, Gold Coast, QLD 4222, Australia;<email>A.Lam@griffith.edu.au</email></nlm:aff></affiliation></author><author><name sortKey="Law, Simon" sort="Law, Simon" uniqKey="Law S" first="Simon" last="Law">Simon Law</name><affiliation><nlm:aff id="af4-biology-08-00075">Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>slaw@hku.hk</email></nlm:aff></affiliation></author><author><name sortKey="Chan, Kwok Wah" sort="Chan, Kwok Wah" uniqKey="Chan K" first="Kwok-Wah" last="Chan">Kwok-Wah Chan</name><affiliation><nlm:aff id="af5-biology-08-00075">Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>kwchan@pathology.hku.hk</email></nlm:aff></affiliation></author><author><name sortKey="Chan, Albert Sun Chi" sort="Chan, Albert Sun Chi" uniqKey="Chan A" first="Albert Sun-Chi" last="Chan">Albert Sun-Chi Chan</name><affiliation><nlm:aff id="af6-biology-08-00075">School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;<email>chenxz3@mail.sysu.edu.cn</email> (A.S.-c.C.);<email>lixsh@mail.sysu.edu.cn</email> (X.L.)</nlm:aff></affiliation></author><author><name sortKey="Li, Xingshu" sort="Li, Xingshu" uniqKey="Li X" first="Xingshu" last="Li">Xingshu Li</name><affiliation><nlm:aff id="af6-biology-08-00075">School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;<email>chenxz3@mail.sysu.edu.cn</email> (A.S.-c.C.);<email>lixsh@mail.sysu.edu.cn</email> (X.L.)</nlm:aff></affiliation></author><author><name sortKey="Lam, Kim Hung" sort="Lam, Kim Hung" uniqKey="Lam K" first="Kim-Hung" last="Lam">Kim-Hung Lam</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Chui, Chung Hin" sort="Chui, Chung Hin" uniqKey="Chui C" first="Chung-Hin" last="Chui">Chung-Hin Chui</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Tang, Johnny Cheuk On" sort="Tang, Johnny Cheuk On" uniqKey="Tang J" first="Johnny Cheuk-On" last="Tang">Johnny Cheuk-On Tang</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno 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type="wicri:Area/Main/Exploration">000891</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells</title><author><name sortKey="Zhou, Yuanyuan" sort="Zhou, Yuanyuan" uniqKey="Zhou Y" first="Yuanyuan" last="Zhou">Yuanyuan Zhou</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Chung, Po Yee" sort="Chung, Po Yee" uniqKey="Chung P" first="Po-Yee" last="Chung">Po-Yee Chung</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Ma, Jessica Yuen Wuen" sort="Ma, Jessica Yuen Wuen" uniqKey="Ma J" first="Jessica Yuen-Wuen" last="Ma">Jessica Yuen-Wuen Ma</name><affiliation><nlm:aff id="af2-biology-08-00075">School of Optometry, The Hong Kong Polytechnic University, Hong Kong 999077, China;<email>majessicayuenwuen@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Lam, Alfred King Yin" sort="Lam, Alfred King Yin" uniqKey="Lam A" first="Alfred King-Yin" last="Lam">Alfred King-Yin Lam</name><affiliation><nlm:aff id="af3-biology-08-00075">Griffith Medical School, Griffith University, Gold Coast, QLD 4222, Australia;<email>A.Lam@griffith.edu.au</email></nlm:aff></affiliation></author><author><name sortKey="Law, Simon" sort="Law, Simon" uniqKey="Law S" first="Simon" last="Law">Simon Law</name><affiliation><nlm:aff id="af4-biology-08-00075">Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>slaw@hku.hk</email></nlm:aff></affiliation></author><author><name sortKey="Chan, Kwok Wah" sort="Chan, Kwok Wah" uniqKey="Chan K" first="Kwok-Wah" last="Chan">Kwok-Wah Chan</name><affiliation><nlm:aff id="af5-biology-08-00075">Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>kwchan@pathology.hku.hk</email></nlm:aff></affiliation></author><author><name sortKey="Chan, Albert Sun Chi" sort="Chan, Albert Sun Chi" uniqKey="Chan A" first="Albert Sun-Chi" last="Chan">Albert Sun-Chi Chan</name><affiliation><nlm:aff id="af6-biology-08-00075">School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;<email>chenxz3@mail.sysu.edu.cn</email> (A.S.-c.C.);<email>lixsh@mail.sysu.edu.cn</email> (X.L.)</nlm:aff></affiliation></author><author><name sortKey="Li, Xingshu" sort="Li, Xingshu" uniqKey="Li X" first="Xingshu" last="Li">Xingshu Li</name><affiliation><nlm:aff id="af6-biology-08-00075">School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;<email>chenxz3@mail.sysu.edu.cn</email> (A.S.-c.C.);<email>lixsh@mail.sysu.edu.cn</email> (X.L.)</nlm:aff></affiliation></author><author><name sortKey="Lam, Kim Hung" sort="Lam, Kim Hung" uniqKey="Lam K" first="Kim-Hung" last="Lam">Kim-Hung Lam</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Chui, Chung Hin" sort="Chui, Chung Hin" uniqKey="Chui C" first="Chung-Hin" last="Chui">Chung-Hin Chui</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author><author><name sortKey="Tang, Johnny Cheuk On" sort="Tang, Johnny Cheuk On" uniqKey="Tang J" first="Johnny Cheuk-On" last="Tang">Johnny Cheuk-On Tang</name><affiliation><nlm:aff id="af1-biology-08-00075">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;<email>yuanyuan.09.zhou@connect.polyu.hk</email> (Y.Z.);</nlm:aff></affiliation></author></analytic><series><title level="j">Biology</title><idno type="eISSN">2079-7737</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author><author><name sortKey="Dikshit, R" uniqKey="Dikshit R">R. Dikshit</name></author><author><name sortKey="Eser, S" uniqKey="Eser S">S. Eser</name></author><author><name sortKey="Mathers, C" uniqKey="Mathers C">C. Mathers</name></author><author><name sortKey="Rebelo, M" uniqKey="Rebelo M">M. Rebelo</name></author><author><name sortKey="Parkin, D M" uniqKey="Parkin D">D.M. Parkin</name></author><author><name sortKey="Forman, D" uniqKey="Forman D">D. 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Wilkinson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Chan, Albert Sun Chi" sort="Chan, Albert Sun Chi" uniqKey="Chan A" first="Albert Sun-Chi" last="Chan">Albert Sun-Chi Chan</name><name sortKey="Chan, Kwok Wah" sort="Chan, Kwok Wah" uniqKey="Chan K" first="Kwok-Wah" last="Chan">Kwok-Wah Chan</name><name sortKey="Chui, Chung Hin" sort="Chui, Chung Hin" uniqKey="Chui C" first="Chung-Hin" last="Chui">Chung-Hin Chui</name><name sortKey="Chung, Po Yee" sort="Chung, Po Yee" uniqKey="Chung P" first="Po-Yee" last="Chung">Po-Yee Chung</name><name sortKey="Lam, Alfred King Yin" sort="Lam, Alfred King Yin" uniqKey="Lam A" first="Alfred King-Yin" last="Lam">Alfred King-Yin Lam</name><name sortKey="Lam, Kim Hung" sort="Lam, Kim Hung" uniqKey="Lam K" first="Kim-Hung" last="Lam">Kim-Hung Lam</name><name sortKey="Law, Simon" sort="Law, Simon" uniqKey="Law S" first="Simon" last="Law">Simon Law</name><name sortKey="Li, Xingshu" sort="Li, Xingshu" uniqKey="Li X" first="Xingshu" last="Li">Xingshu Li</name><name sortKey="Ma, Jessica Yuen Wuen" sort="Ma, Jessica Yuen Wuen" uniqKey="Ma J" first="Jessica Yuen-Wuen" last="Ma">Jessica Yuen-Wuen Ma</name><name sortKey="Tang, Johnny Cheuk On" sort="Tang, Johnny Cheuk On" uniqKey="Tang J" first="Johnny Cheuk-On" last="Tang">Johnny Cheuk-On Tang</name><name sortKey="Zhou, Yuanyuan" sort="Zhou, Yuanyuan" uniqKey="Zhou Y" first="Yuanyuan" last="Zhou">Yuanyuan Zhou</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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