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

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 (<b>11</b>) and 3-pyridyl-4'-aminochalcone (<b>17</b>). 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 <b>11</b> and <b>17</b> were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested <b>11</b> and <b>17</b> upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones <b>11</b> and <b>17</b> can define their <i>in vivo</i> therapeutic potential.