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

Author(s):Show less -

dos Santos, Mariana Bastos ^[1] ; Anselmo, Daiane Bertholin ^[1] ; de Oliveira, Jessica Gisleine ^[2] ; Jardim-Perassi, Bruna V. ^[2] ; Monteiro, Diego Alves ^[3] ; Silva, Gabriel ^[4] ; Gomes, Eleni ^[3] ; Fachin, Ana Lucia ^[4] ; Marins, Mozart ^[4] ; Pires de Campos Zuccari, Debora Aparecida ^[2] ; Regasini, Luis Octavio ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Dept Chem & Environm Chem, Inst Biosci Humanities & Exact Sci IBILCE, Sao Paulo - Brazil

^[2] Med Coll Sao Jose do Rio Preto FAMERP, Dept Mol Biol, Sao Paulo - Brazil

^[3] Sao Paulo State Univ UNESP, Dept Biol, Inst Biosci Humanities & Exact Sci IBILCE, Sao Paulo - Brazil

^[4] Univ Ribeirao Preto UNAERP, Biotechnol Unit, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 34, n. 1, p. 1093-1099, JAN 1 2019.
• Web of Science Citations: 1

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 mu M 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. (AU)

• FAPESP's process: 18/15083-2 - Synthesis and biological evaluation of isobavachalcone (IBC) and analogs as potential agents against tuberculosis
• Grantee: Luis Octávio Regasini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/18330-0 - Synthesis and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors
• Grantee: Luis Octávio Regasini
• Support Opportunities: Regular Research Grants