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Studies compared COP and its effects with doxorubicin (DOX) in multiple breast cell lines, including sensitive and DOX-resistant models. Cytotoxicity, drug-resistance metrics, transporter efflux activity, and ABCT gene expression were quantified using MTT, combination analyses, flow cytometry, and RT-PCR. COP showed synergistic enhancement of DOX efficacy, increased intracellular tracer accumulation, reduced efflux, and downregulated key ABCT genes and proteins.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/coptisine-enhances-the-sensitivity-of-chemoresistant-breast-cancer-cells-by-inhibiting-the-function-and-expression-of-abc-transporters-original-research/331641/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/coptisine-enhances-the-sensitivity-of-chemoresistant-breast-cancer-cells-by-inhibiting-the-function-and-expression-of-abc-transporters-original-research/331641.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address in breast cancer treatment?","Question",{"text":113,"@type":114},"The study addresses multidrug resistance (MDR) in breast cancer, mainly driven by ABC transporters that reduce the effectiveness of anticancer drugs such as doxorubicin.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was coptisine tested for reversing doxorubicin resistance?",{"text":118,"@type":114},"Cytotoxicity and DOX sensitization were measured using the MTT assay, and DOX resistance reversal was evaluated using resistance ratio (RR), combination index (CI), and isobologram analysis (IB).",{"name":120,"@type":111,"acceptedAnswer":121},"Which ABC transporters and outcomes were assessed?",{"text":122,"@type":114},"The study assessed ABCT efflux function and intracellular accumulation using Rho123 with flow cytometry, and evaluated gene expression of P-gp/MDR1, BCRP, and MRP1 using RT-PCR; it also reported downregulation of ABCT gene and protein expression with COP plus DOX.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},331641,1790375559,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Original Research PUBLISHED 03 December 2024 DOI 10.3389/fphar.2024.1472458  \nOPEN ACCESS  \nEDITED BY  \nHeike Wulff,  \nUniversity of California, Davis, United States  \nREVIEWED BY  \nNoor Ayad Hussein,  \nStanford University, United States Wangbin Wu,  \nUniversity of Nebraska Medical Center, United States  \n*CORRESPONDENCE  \nSafaa Yehia Eid,  \n [syeid@uqu.edu.sa](syeid@uqu.edu.sa)  \nRECEIVED 29 July 2024  \nACCEPTED 21 November 2024  \nPUBLISHED 03 December 2024  \nCITATION  \nEid SY (2024) Coptisine enhances the sensitivity of chemoresistant breast cancer cells by inhibiting the function and expression of ABC transporters.  \nFront. Pharmacol. 15:1472458 .  \ndoi: 10.3389/fphar.2024.1472458  \nCOPYRIGHT  \n© 2024 Eid. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nCoptisine enhances the sensitivity of chemoresistant breast cancer cells by inhibiting the function and expression of ABC transporters  \nSafaa Yehia Eid*  \nDepartment of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia  \nBackground: Multidrug resistance (MDR), mainly caused by ATP-binding cassette transporters (ABCTs) efflux, makes it difficult for many anticancer drugs to treat breast cancer(BC) . Phytochemicalscan reverse cancer’sMDR by modifying ABC transporter expression and function, as well as working synergistically with anticancer drugs to target other molecules. The reversal effect of the isoquinoline alkaloid coptisine(COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDBMB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR.  \nMethods: The cytotoxicity of COP and its ability to improve doxorubicin (DOX) cytotoxicity were assessed using the MTT assay. The effectiveness of COP in reversing DOX resistance was evaluated by calculating resistance ratio (RR) values, combination index (CI), and isobologram (IB). The inhibitory effect of COP on ABCTefflux function in comparison to verapamil (VER) was evaluated by measuring the cellular accumulation of Rho123 using flow cytometry. The impact of COP, either alone or in combination with DOX, on the gene expression of ABCTs (P-gp/MDR1, BCRP, and MRP1) of investigated cell lines was assessed by RT-PCR.  \nResults: The COP showed modest cytotoxicity on the examined cell lines. In MCF-7/ADR and MDA-MB-231/ADR cells, COP (31 μM) enhanced DOX cytotoxicity with CI (0.77 and 0.75), RR (2.58 and 3.33), and IB suggesting synergism. COP significantly inhibits ABCT function in resistant BC cell lines, increases Rho123 accumulation, and decreases efflux more than VER; 2 . 1 and 1 .2-fold, respectively. The combination of COP and DOX had a strong inhibitory effect on ABCT function (3 . 1 and 3 . 9 times VER, P\u003C 0. 001) and downregulated the genes and protein expression of ABCT.  \nConclusion: COP reversed ABCT-mediated multidrug resistance in vitro, indicating its potential as a multidrug resistance-reversing agent in cancer chemotherapy.  \nKEYWORDS  \ncoptisine, multidrug resistance, ABC-transporters, breast cancer, P-glycoprotein  \n1 Introductions  \nBreast cancer (BC) is a malignancy commonly detected in women, characterized by asignificant global mortality rate. The global incidence of breast cancer reached 2.3 million cases in 2022 (Ferlay J et al., 2024) . As the most often diagnosed cancer in females, it represents around 23% of all cancer cases (Trapani et al., 2022) . The molecular differences  \nFrontiers in Ph","cbCaigKZIaMf9qUP","https://ap.wps.com/l/cbCaigKZIaMf9qUP","pdf",4130206,13,"English","# Background\n# Methods\n# Results\n# Conclusion\n# Keywords\n# Introduction","[{\"question\":\"What problem does the study address in breast cancer treatment?\",\"answer\":\"The study addresses multidrug resistance (MDR) in breast cancer, mainly driven by ABC transporters that reduce the effectiveness of anticancer drugs such as doxorubicin.\"},{\"question\":\"How was coptisine tested for reversing doxorubicin resistance?\",\"answer\":\"Cytotoxicity and DOX sensitization were measured using the MTT assay, and DOX resistance reversal was evaluated using resistance ratio (RR), combination index (CI), and isobologram analysis (IB).\"},{\"question\":\"Which ABC transporters and outcomes were assessed?\",\"answer\":\"The study assessed ABCT efflux function and intracellular accumulation using Rho123 with flow cytometry, and evaluated gene expression of P-gp/MDR1, BCRP, and MRP1 using RT-PCR; it also reported downregulation of ABCT gene and protein expression with COP plus DOX.\"}]","Coptisine enhances the sensitivity of chemoresistant breast cancer cells by inhibiting the function and expression of ABC transporters - Original Research | PDF",1789994418,33]