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

Journal of Enzyme Inhibition and Medicinal Chemistry

Mozart Marins¹  Gabriel Silva¹  Ana Lucia Fachin¹  Diego Alves Monteiro²  Eleni Gomes²  Daiane Bertholin Anselmo³  Mariana Bastos dos Santos³  Luis Octavio Regasini³  Débora Aparecida Pires de Campos Zuccari⁴  Jéssica Gisleine de Oliveira⁴  Bruna V. Jardim-Perassi⁴ 

[1]Biotechnology Unit, University of Ribeirão Preto (UNAERP), São Paulo, Brazi

[2]Department of Biology, Institute of Biosciences, Humanities and Exact Sciences (IBILCE), São Paulo State University (UNESP), São Paulo, Brazil

[3]Department of Chemistry and Environmental Chemistry, Institute of Biosciences, Humanities and Exact Sciences (IBILCE), São Paulo State University (UNESP), São Paulo, Brazil

[4]Department of Molecular Biology, Medicine College of São José do Rio Preto (FAMERP), São Paulo, Brazil

关键词: Chalcones;    cancer;    p53;    antiproliferative;    apoptosis;   

DOI  :  10.1080/14756366.2019.1615485

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY