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

J Enzyme Inhib Med Chem. 2019 Dec;34(1):1093-1099. doi: 10.1080/14756366.2019.1615485.

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.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Chalcones / chemical synthesis
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects*

Substances

  • Antineoplastic Agents
  • Chalcones
  • Tumor Suppressor Protein p53

Grants and funding

The authors gratefully acknowledge financial support from Coordination for Improvement of Higher Education Personnel (CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001), Brazilian Council for Scientific and Technological Development (CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grants # 471129/2013–5, 306251/2016–7 and 429322/2018–6); São Paulo Research Foundation (FAPESP, Fundação de Amparo a Pesquisa do Estado de São Paulo, Grants # 2014/18330–0 and 2018/15083–2).