{"doi":"10.1007/s11095-008-9793-y","title":"Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein","abstract":null,"journal":"Pharmaceutical Research","year":2009,"id":677671,"datarank":0.6766289259775276,"base_score":4.51085950651685,"endowment":4.51085950651685,"self_citation_contribution":0.6766289259775276,"citation_network_contribution":0.0,"self_endowment_contribution":0.6766289259775276,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1770643,"name":"Gang Jun Du","orcid":null,"position":1,"is_corresponding":false},{"id":226446,"name":"Ling Zhang","orcid":"0000-0001-8371-5252","position":2,"is_corresponding":false},{"id":1770645,"name":"Chun Ling Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":1770646,"name":"Wan Liang Lu","orcid":null,"position":4,"is_corresponding":false},{"id":801116,"name":"Wei Liang","orcid":"0000-0002-0739-6648","position":5,"is_corresponding":false},{"id":1770641,"name":"Fa Yun Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein","abstract":"<h4>Purpose</h4>Naringenin has shown paradoxical results to modulate the function of multidrug resistance-associated proteins (MRPs). The aim of this study is to interpret whether naringenin can reverse intrinsic and/or acquired resistance of cancer cells to chemotherapeutic agents.<h4>Methods</h4>The effects of naringenin on the uptake, retention and cytotoxicity of doxorubicin were investigated in A549, MCF-7, HepG2 and MCF-7/DOX cells. Cellular efflux pathways modulated by naringenin were assessed with their specific substrates and inhibitors. The improved antitumor activity of doxorubicin in combination with naringenin was also investigated in vivo.<h4>Results</h4>The IC(50) values of doxorubicin in combination with naringenin in A549 and MCF-7 cells were approximately 2-fold lower than that of doxorubicin alone. The increased sensitivity to doxorubicin by naringenin in HepG2 and MCF-7/DOX cells was not observed. Naringenin increased the cellular doxorubicin accumulation through inhibiting doxorubicin efflux in the cells expressing MRPs but not P-gp. In contrast to doxorubicin alone, doxorubicin in combination with naringenin enhanced antitumor activity in vivo with low systemic toxicity.<h4>Conclusion</h4>Naringenin enhances antitumor effect of doxorubicin by selective modulating drug efflux pathways. Naringenin will be a useful adjunct to improve the effectiveness of chemotherapeutic agents in treatment of human cancers.","is_dataset_classified":null,"base_score":4.51085950651685,"endowment":4.51085950651685,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19067124","pmcid":null,"openalex_id":"https://openalex.org/W2151132253","authors":[],"funders":[],"total_grants":0,"fwci":0.4296,"citation_percentile":0.66086452,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":5},{"year":2014,"count":6},{"year":2015,"count":7},{"year":2016,"count":5},{"year":2017,"count":2},{"year":2018,"count":8},{"year":2019,"count":6},{"year":2020,"count":8},{"year":2021,"count":9},{"year":2022,"count":9},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"closed","license":"http://www.springer.com/tdm","oa_locations":[{"url":"http://link.springer.com/content/pdf/10.1007/s11095-008-9793-y.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1007/s11095-008-9793-y/fulltext.html","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1007/s11095-008-9793-y","host_type":"publisher"},{"url":"https://doi.org/10.1007/s11095-008-9793-y","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19067124","host_type":"repository"}],"fields_of_study":["Drug Transport and Resistance Mechanisms","Metal complexes synthesis and properties","Protein Interaction Studies and Fluorescence Analysis"],"mesh_terms":["Animals","Antibiotics, Antineoplastic","Biological Transport","Cell Survival","Dose-Response Relationship, Drug","Doxorubicin","Female","Humans","Mice, Inbred C57BL","Neoplasms","RNA, Messenger","Time Factors","ATP Binding Cassette Transporter, Subfamily B","Drug Resistance, Neoplasm","Inhibitory Concentration 50","ATP Binding Cassette Transporter, Subfamily B, Member 1","Xenograft Model Antitumor Assays","Multidrug Resistance-Associated Proteins","ATP-Binding Cassette, Sub-Family C Proteins","Flavanones","Cell Line, Tumor","Cell Proliferation","Mice"],"keywords":["Naringenin","Doxorubicin","Pharmacology","Efflux","In vivo","Chemistry","P-glycoprotein","Multiple drug resistance","Cytotoxicity","In vitro","Biochemistry","Biology","Medicine","Chemotherapy","Internal medicine","Flavonoid","Antibiotics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T04:23:40.863071Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}