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

Autor(es)

Afonso de Lima, Carolina ^[1] ; de Souza Bueno, Ian Lucas ^[1] ; Nunes Siqueira Vasconcelos, Stanley ^{[2, 3, 4]} ; Sciani, Juliana Mozer ^[5] ; Ruiz, Ana Lucia Tasca Gois ^[6] ; Foglio, Mary Ann ^[6] ; de Carvalho, Joao Ernesto ^[6] ; Barbarini Longato, Giovanna ^[1]

Afiliação do(s) autor(es)

^[1] Sao Francisco Univ, Res Lab Mol Pharmacol & Bioact Cpds, BR-12916900 Braganca Paulista, SP - Brazil

^[2] Univ Campinas UNICAMP, Ctr Mol Biol & Genet Engn CBMEG, BR-13083875 Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Ctr Med Chem CQMED, BR-13083875 Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, Struct Genom Consortium, Dept Genet & Evolut, Inst Biol IB, BR-3083866 Campinas, SP - Brazil

^[5] Sao Francisco Univ, Lab Multidisciplinary Res, BR-12916900 Braganca Paulista, SP - Brazil

^[6] Univ Estadual Campinas, LAFTEx Fac Pharmaceut Sci, BR-13083859 Braganca Paulista, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 13, n. 10 OCT 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 10/50232-7 - Atividade anticancer e mecanismo de acao de compostos isolados das folhas de piper regnellii (miq.) c. dc. var. regnellii
• Beneficiário: Giovanna Barbarini Longato
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/09475-5 - Novas abordagens para inibidores de proteínas quinases MRCKa, MRCKb E MRCKg
• Beneficiário: Stanley Nunes Siqueira Vasconcelos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/06137-6 - Bioprospecção de compostos naturais e derivados bioativos com potencial atividade anticâncer: ensaios in vitro/in vivo e investigação do mecanismo de ação.
• Beneficiário: Giovanna Barbarini Longato
• Modalidade de apoio: Auxílio à Pesquisa - Regular