Antiproliferative and pro-apoptotic activities of 2'- and 4'-aminochalcones against tumor canine cells

Eur J Med Chem. 2017 Sep 29:138:884-889. doi: 10.1016/j.ejmech.2017.06.049. Epub 2017 Jun 27.

Abstract

In the present study, a series of 2'- and 4'-aminochalcones were synthesized and their antiproliferative activity against a canine malignant histiocytic cell line (DH82) was evaluated. Particularly aminochalcones with a hydrophobic substituent on ring B proved to be potent antiproliferative agents. Among these compounds, aminochalcones 3, 4 and 11 inhibited the growth of DH82 cells, with IC50 values of 34.4, 31.4 and 38.2 μM, respectively, and were three times more potent than etoposide (IC50 = 95.5 μM). The selected chalcones induced death through apoptosis rather than necrosis in DH82 and non-tumorigenic Madin-Darby canine kidney cells (MDCK). Further experiments suggested that the aminochalcones interfere with the regulation of oncogenes/tumor suppressor genes. Aminochalcone 11 inhibited transcription of the TOPOIIα and TP53 genes and aminochalcone 4 down-regulated Sp1 protein expression in a concentration-dependent manner.

Keywords: Antiproliferative; Apoptosis; Canine cancer; Chalcone.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Chalcones / chemical synthesis
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Madin Darby Canine Kidney Cells / drug effects*
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Chalcones