Effects of Propolis and Phenolic Acids on Triple-Negative Breast Cancer Cell Lines: Potential Involvement of Epigenetic Mechanisms

Autor(es)

Maia Assumpcao, Joao Henrique ^[1] ; Sekijima Takeda, Agnes Alessandra ^[2] ; Sforcin, Jose Mauricio ^[1] ; Rainho, Claudia Aparecida ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Chem & Biol Sci, Botucatu 18618689, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Biosci, Dept Biophys & Pharmacol, Botucatu 18618689, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 25, n. 6 MAR 2 2020.
• Citações Web of Science: 0

Resumo

Triple-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 well-known 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. (AU)

• Processo FAPESP: 07/59110-9 - Controle epigenetico da expressao genica na carcinogenese mamaria: investigacao de genes candidatos a supressores tumorais mapeados em 3p21.3.
• Beneficiário: Claudia Aparecida Rainho
• Modalidade de apoio: Auxílio à Pesquisa - Regular