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Article

Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies

1
Research Laboratory in Molecular Pharmacology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo 12916-900, Brazil
2
Center for Medicinal Chemistry (CQMED), University of Campinas (UNICAMP), Campinas, São Paulo 13083-875, Brazil
3
Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo 13083-875, Brazil
4
Structural Genomics Consortium, Department of Genetics and Evolution, Institute of Biology (IB), University of Campinas (UNICAMP), Campinas, São Paulo 3083-866, Brazil
5
Laboratory of Multidisciplinary Research, São Francisco University, Bragança Paulista, São Paulo 12916-900, Brazil
6
LAFTEx Faculty of Pharmaceutical Science, University of Campinas, Campinas, São Paulo 13083-859, Brazil
*
Author to whom correspondence should be addressed.
Contributed equally.
Pharmaceuticals 2020, 13(10), 327; https://doi.org/10.3390/ph13100327
Received: 26 August 2020 / Revised: 21 September 2020 / Accepted: 9 October 2020 / Published: 21 October 2020
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants)
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’s 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. View Full-Text
Keywords: multidrug resistance; glycoprotein-P; apiole; in silico; druglikeness multidrug resistance; glycoprotein-P; apiole; in silico; druglikeness
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MDPI and ACS Style

Afonso de Lima, C.; de Souza Bueno, I.L.; Nunes Siqueira Vasconcelos, S.; Sciani, J.M.; Ruiz, A.L.T.G.; Foglio, M.A.; Carvalho, J.E.d.; Barbarini Longato, G. Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies. Pharmaceuticals 2020, 13, 327. https://doi.org/10.3390/ph13100327

AMA Style

Afonso de Lima C, de Souza Bueno IL, Nunes Siqueira Vasconcelos S, Sciani JM, Ruiz ALTG, Foglio MA, Carvalho JEd, Barbarini Longato G. Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies. Pharmaceuticals. 2020; 13(10):327. https://doi.org/10.3390/ph13100327

Chicago/Turabian Style

Afonso de Lima, Carolina, Ian L. de Souza Bueno, Stanley Nunes Siqueira Vasconcelos, Juliana M. Sciani, Ana L.T.G. Ruiz, Mary A. Foglio, João E.d. Carvalho, and Giovanna Barbarini Longato. 2020. "Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies" Pharmaceuticals 13, no. 10: 327. https://doi.org/10.3390/ph13100327

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