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dc.contributor.authorAssumpção, João Henrique Maia [UNESP]
dc.contributor.authorTakeda, Agnes Alessandra Sekijima [UNESP]
dc.contributor.authorSforcin, José Maurício [UNESP]
dc.contributor.authorRainho, Cláudia Aparecida [UNESP]
dc.date.accessioned2020-12-12T02:37:20Z
dc.date.available2020-12-12T02:37:20Z
dc.date.issued2020-03-02
dc.identifierhttp://dx.doi.org/10.3390/molecules25061289
dc.identifier.citationMolecules, v. 25, n. 6, 2020.
dc.identifier.issn1420-3049
dc.identifier.urihttp://hdl.handle.net/11449/201618
dc.description.abstractTriple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy. Evidence supports that small molecules showing DNA methyltransferase inhibitory activity (DNMTi) are important to sensitize cancer cells to cytotoxic agents, in part, by reverting the acquired epigenetic changes associated with the resistance to therapy. The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs (epi-drugs). We selected three phenolic acids (caffeic, dihydrocinnamic, and p-coumaric) commonly detected in propolis and the (-)-epigallocatechin-3-gallate (EGCG) from green tea, which is a wellknown DNA demethylating agent, for further analysis. The treatment with p-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor S-Adenosyl-L-homocysteine (SAH). Although the ethanolic extract of propolis (EEP) did not change the global DNA methylation content, by using MS-PCR (Methylation-Specific Polymerase Chain Reaction) we demonstrated that EEP and EGCG were able to partly demethylate the promoter region of RASSF1A in BT-549 cells. Also, in vitro treatment with EEP altered the RASSF1 protein expression levels. Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressor RASSF1A. These findings suggest that propolis are a promising source for epi-drugs discovery.en
dc.language.isoeng
dc.relation.ispartofMolecules
dc.sourceScopus
dc.subjectDNA methylation
dc.subjectDNA methyltransferase inhibitors
dc.subjectEGCG
dc.subjectEpigenetic therapy
dc.subjectMolecular docking
dc.subjectRASSF1
dc.titleEffects of propolis and phenolic acids on triple-negative breast cancer cell lines: Potential involvement of epigenetic mechanismsen
dc.typeArtigo
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.description.affiliationDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationDepartment of Biophysics and Pharmacology Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Biophysics and Pharmacology Institute of Biosciences São Paulo State University (UNESP)
dc.identifier.doi10.3390/molecules25061289
dc.identifier.scopus2-s2.0-85081657463
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