{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:01:03Z","timestamp":1787695263629,"version":"build-2784847793"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2010\/50232-7"],"award-info":[{"award-number":["2010\/50232-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/06137\u20136"],"award-info":[{"award-number":["2016\/06137\u20136"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/09475-5"],"award-info":[{"award-number":["2018\/09475-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound\u2019s relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/ph13100327","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T10:27:58Z","timestamp":1603362478000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies"],"prefix":"10.3390","volume":"13","author":[{"given":"Carolina","family":"Afonso de Lima","sequence":"first","affiliation":[{"name":"Research Laboratory in Molecular Pharmacology and Bioactive Compounds, S\u00e3o Francisco University, Bragan\u00e7a Paulista, S\u00e3o Paulo 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Lucas","family":"de Souza Bueno","sequence":"additional","affiliation":[{"name":"Research Laboratory in Molecular Pharmacology and Bioactive Compounds, S\u00e3o Francisco University, Bragan\u00e7a Paulista, S\u00e3o Paulo 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7289-5753","authenticated-orcid":false,"given":"Stanley","family":"Nunes Siqueira Vasconcelos","sequence":"additional","affiliation":[{"name":"Center for Medicinal Chemistry (CQMED), University of Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-875, Brazil"},{"name":"Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-875, Brazil"},{"name":"Structural Genomics Consortium, Department of Genetics and Evolution, Institute of Biology (IB), University of Campinas (UNICAMP), Campinas, S\u00e3o Paulo 3083-866, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-206X","authenticated-orcid":false,"given":"Juliana Mozer","family":"Sciani","sequence":"additional","affiliation":[{"name":"Laboratory of Multidisciplinary Research, S\u00e3o Francisco University, Bragan\u00e7a Paulista, S\u00e3o Paulo 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-8702","authenticated-orcid":false,"given":"Ana L\u00facia Tasca Gois","family":"Ruiz","sequence":"additional","affiliation":[{"name":"LAFTEx Faculty of Pharmaceutical Science, University of Campinas, Campinas, S\u00e3o Paulo 13083-859, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"Foglio","sequence":"additional","affiliation":[{"name":"LAFTEx Faculty of Pharmaceutical Science, University of Campinas, Campinas, S\u00e3o Paulo 13083-859, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Ernesto de","family":"Carvalho","sequence":"additional","affiliation":[{"name":"LAFTEx Faculty of Pharmaceutical Science, University of Campinas, Campinas, S\u00e3o Paulo 13083-859, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-8957","authenticated-orcid":false,"given":"Giovanna","family":"Barbarini Longato","sequence":"additional","affiliation":[{"name":"Research Laboratory in Molecular Pharmacology and Bioactive Compounds, S\u00e3o Francisco University, Bragan\u00e7a Paulista, S\u00e3o Paulo 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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