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. 2019 Dec;34(1):1093-1099.
doi: 10.1080/14756366.2019.1615485.

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Mariana Bastos Dos Santos  1 , Daiane Bertholin Anselmo  1 , Jéssica Gisleine de Oliveira  2 , Bruna V Jardim-Perassi  2 , Diego Alves Monteiro  3 , Gabriel Silva  4 , Eleni Gomes  3 , Ana Lucia Fachin  4 , Mozart Marins  4 , Débora Aparecida Pires de Campos Zuccari  2 , Luis Octavio Regasini  1
Affiliations

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Mariana Bastos Dos Santos et al. J Enzyme Inhib Med Chem. 2019 Dec.

Abstract

Chalcones are valuable structures for drug discovery due to their broad bioactivity spectrum. In this study, we evaluated 20 synthetic chalcones against estrogen-receptor-positive breast cancer cells (MCF-7 line) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 line). Antiproliferative screening by MTT assay resulted in two most active compounds: 2-fluoro-4'-aminochalcone (11) and 3-pyridyl-4'-aminochalcone (17). Their IC50 values ranged from 13.2 to 34.7 µM against both cell lines. Selected chalcones are weak basic compounds and maintained their antiproliferative activity under acidosis conditions (pH 6.7), indicating their resistance to ion-trapping effect. The mode of breast cancer cells death was investigated and chalcones 11 and 17 were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested 11 and 17 upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones 11 and 17 can define their in vivo therapeutic potential.

Keywords: Chalcones; antiproliferative; apoptosis; cancer; p53.

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Figures

Scheme 1.
Scheme 1.
Claisen-Schmidt reaction for synthesis of chalcones 1–20.
Figure 1.
Figure 1.
Percentage of metabolically viable cells (%MVC) under acidosis. (a) treatments with selected chalcones 11 and 17 against MCF-7 line; (b) treatments with selected chalcones 11 and 17 against MDA-MB-231 line. Different letters in the graph indicate statistical difference with significance p< 0.05 in Tukey’s multiple comparisons test. DMSO 0.1% was used as negative control.
Figure 2.
Figure 2.
Pro-apoptotic activity of selected chalcones 11 and 17 towards MCF-7 (a) and MDA-MB-231 (b) cells. Different letters indicate statistical difference with significance p< 0.05 in Tukey’s multiple comparisons test. DMSO 0.1% was used as a vehicle control.
Figure 3.
Figure 3.
Effect of selected chalcones 11 and 17 on Sp1 and p53 proteins expression in MCF-7 cell line.
See this image and copyright information in PMC

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