Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 6
Document type: Journal article
Source: PHARMACEUTICALS; v. 13, n. 10 OCT 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 18/09475-5 - New approaches to inhibitors for protein kinases MRCKa, MRCKb AND MRCKg
Grantee:Stanley Nunes Siqueira Vasconcelos
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 16/06137-6 - Bioprospecting for natural compounds and bioactive derivatives with potent anticancer activity: in vitro/in vivo assays and investigation into the mechanism of action.
Grantee:Giovanna Barbarini Longato
Support Opportunities: Regular Research Grants