Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest

Autor(es)

Buso Bortolotto, Luis Felipe ; Barbosa, Flavia Regina ; Silva, Gabriel ; Bitencourt, Tamires Aparecida ; Beleboni, Rene Oliveira ; Baek, Seung Joon ; Marins, Mozart ; Fachin, Ana Lucia

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 85, p. 425-433, JAN 2017.
• Citações Web of Science: 20

Resumo

Chalcones are precursors of flavonoids that exhibit structural heterogeneity and potential antitumor activity. The objective of this study was to characterize the cytotoxicity of trans-chalcone and licochalcone A (LicoA(1)) against a breast cancer cell line (MCF-7) and normal murine fibroblasts (3T3). Also the mechanisms of the anti-cancer activity of these two compounds were studied. The alkaline comet assay revealed dose-dependent genotoxicity, which was more responsive against the tumor cell line, compared to the 3T3 mouse fibroblast cell line. Flow cytometry showed that the two chalcones caused the cell cycle arrest in the G1 phase and induced apoptosis in MCF-7 cells. Using PCR Array, we found that trans-chalcone and LicoA trigger apoptosis mediated by the intrinsic pathway as demonstrated by the inhibition of Bcl-2 and induction of Bax. In western blot assay, the two chalcones reduced the expression of cell death-related proteins such as Bcl-2 and cyclin D1 and promoted the cleavage of PARP. However, only trans-chalcone induced the expression of the CIDEA gene and protein in these two experiments. Furthermore, transient transfections of MCF-7 using a construction of a promoter-luciferase vector showed that trans-chalcone induced the expression of the CIDEA promoter activity in 24 and 48 h. In conclusion, the results showed that trans-chalcone promoted high induction of the CIDEA promoter gene and protein, which is related to DNA fragmentation during apoptosis. (C) 2016 Published by Elsevier Masson SAS. (AU)

• Processo FAPESP: 12/06889-7 - Diversidade genética de Solanum lycocarpum e estudo fitoquímico direcionado na busca de ativos antimicrobianos e no potencial citotóxico e genotóxico de alcalóides
• Beneficiário: Ana Lucia Fachin Saltoratto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/02920-7 - Transcriptoma do dermatófito Trichophyton rubrum em resposta ao antifúngico transchalcona em condições de cultivo que simulam a infecção
• Beneficiário: Tamires Aparecida Bitencourt
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/15862-5 - Análise celular e molecular da resposta de células tumorais ao efeito de chalconas
• Beneficiário: Luis Felipe Buso Bortolotto
• Modalidade de apoio: Bolsas no Brasil - Mestrado