{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362262943526760192.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1007/s00280-007-0426-7"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/content/pdf/10.1007/s00280-007-0426-7.pdf"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/article/10.1007/s00280-007-0426-7/fulltext.html"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/content/pdf/10.1007/s00280-007-0426-7"}},{"identifier":{"@type":"PMID","@value":"17345086"}}],"dc:title":[{"@value":"Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: transporter specificity and structure–activity relationship"}],"description":[{"notation":[{"@value":"ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-related protein 1 (MRP1), confer resistance to various anticancer agents. We previously reported that some flavonoids have BCRP-inhibitory activity. Here we show the reversal effects of an extensive panel of flavonoids upon BCRP-, P-gp-, and MRP1-mediated drug resistance.Reversal effects of flavonoids upon BCRP-, P-gp-, or MRP1-mediated drug resistance were examined in the BCRP- or MDR1-transduced human leukemia K562 cells or in the MRP1-transfected human epidermoid carcinoma KB-3-1 cells using cell growth inhibition assays. The IC(50) values were determined from the growth inhibition curves. The RI(50) values were then determined as the concentration of inhibitor that causes a twofold reduction of the IC(50) in each transfectant. The reversal of BCRP activity was tested by measuring the fluorescence of intracellular topotecan.The BCRP-inhibitory activity of 32 compounds was screened, and 20 were found to be active. Among these active compounds, 3',4',7-trimethoxyflavone showed the strongest anti-BCRP activity with RI(50) values of 0.012 microM for SN-38 and 0.044 muM for mitoxantrone. We next examined the effects of a panel of 11 compounds on P-gp- and MRP1-mediated drug resistance. Two of the flavones, 3',4',7-trimethoxyflavone and acacetin, showed only low anti-P-gp activity, with the remainder displaying no suppressive effects against P-gp. None of the flavonoids that we tested inhibited MRP1.Our present results thus indicate that many flavonoids selectively inhibit BCRP only. Moreover, we examined the structure-BCRP inhibitory activity relationship from our current study."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382262943526760194","@type":"Researcher","foaf:name":[{"@value":"Kazuhiro Katayama"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943526760192","@type":"Researcher","foaf:name":[{"@value":"Kazuto Masuyama"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943526760195","@type":"Researcher","foaf:name":[{"@value":"Sho Yoshioka"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943526760193","@type":"Researcher","foaf:name":[{"@value":"Hitomi Hasegawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943526760196","@type":"Researcher","foaf:name":[{"@value":"Junko Mitsuhashi"}]},{"@id":"https://cir.nii.ac.jp/crid/1030003658329348096","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10179161"},{"@type":"NRID","@value":"1000010179161"},{"@type":"NRID","@value":"9000001262888"},{"@type":"NRID","@value":"9000001090894"},{"@type":"NRID","@value":"9000009856610"},{"@type":"NRID","@value":"9000000689348"},{"@type":"NRID","@value":"9000415171559"},{"@type":"NRID","@value":"9000010529719"},{"@type":"NRID","@value":"9000001707212"},{"@type":"NRID","@value":"9000001726168"},{"@type":"NRID","@value":"9000257910165"},{"@type":"NRID","@value":"9000258049963"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0194875"}],"foaf:name":[{"@value":"Yoshikazu Sugimoto"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03445704"},{"@type":"EISSN","@value":"14320843"}],"prism:publicationName":[{"@value":"Cancer Chemotherapy and Pharmacology"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2007-03-08","prism:volume":"60","prism:number":"6","prism:startingPage":"789","prism:endingPage":"797"},"reviewed":"false","dc:rights":["http://www.springer.com/tdm"],"url":[{"@id":"http://link.springer.com/content/pdf/10.1007/s00280-007-0426-7.pdf"},{"@id":"http://link.springer.com/article/10.1007/s00280-007-0426-7/fulltext.html"},{"@id":"http://link.springer.com/content/pdf/10.1007/s00280-007-0426-7"}],"createdAt":"2007-03-07","modifiedAt":"2025-01-14","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Flavonoids","dc:title":"Flavonoids"},{"@id":"https://cir.nii.ac.jp/all?q=Antineoplastic%20Agents,%20Hormonal","dc:title":"Antineoplastic Agents, Hormonal"},{"@id":"https://cir.nii.ac.jp/all?q=Dose-Response%20Relationship,%20Drug","dc:title":"Dose-Response Relationship, Drug"},{"@id":"https://cir.nii.ac.jp/all?q=Biological%20Transport","dc:title":"Biological Transport"},{"@id":"https://cir.nii.ac.jp/all?q=Flavones","dc:title":"Flavones"},{"@id":"https://cir.nii.ac.jp/all?q=Neoplasm%20Proteins","dc:title":"Neoplasm Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Inhibitory%20Concentration%2050","dc:title":"Inhibitory Concentration 50"},{"@id":"https://cir.nii.ac.jp/all?q=Structure-Activity%20Relationship","dc:title":"Structure-Activity Relationship"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Resistance,%20Neoplasm","dc:title":"Drug Resistance, Neoplasm"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line,%20Tumor","dc:title":"Cell Line, Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=ATP%20Binding%20Cassette%20Transporter,%20Subfamily%20G,%20Member%202","dc:title":"ATP Binding Cassette Transporter, Subfamily G, Member 2"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=ATP-Binding%20Cassette%20Transporters","dc:title":"ATP-Binding Cassette Transporters"},{"@id":"https://cir.nii.ac.jp/all?q=ATP%20Binding%20Cassette%20Transporter,%20Subfamily%20B,%20Member%201","dc:title":"ATP Binding Cassette Transporter, Subfamily B, Member 1"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Screening%20Assays,%20Antitumor","dc:title":"Drug Screening Assays, Antitumor"},{"@id":"https://cir.nii.ac.jp/all?q=Multidrug%20Resistance-Associated%20Proteins","dc:title":"Multidrug Resistance-Associated Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=K562%20Cells","dc:title":"K562 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Topotecan","dc:title":"Topotecan"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Proliferation","dc:title":"Cell Proliferation"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360283693122892160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of <scp>AKT</scp>3 expression on <scp>MYC</scp>‐ and caspase‐8‐dependent apoptosis caused by polo‐like 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