Cytotoxic effect of a family of peroxisome proliferator-activated receptor antagonists in colorectal and pancreatic cancer cell lines

Chem Biol Drug Des. 2017 Nov;90(5):1029-1035. doi: 10.1111/cbdd.13026. Epub 2017 Jul 19.

Abstract

Recent studies report an interesting role of peroxisome proliferator-activated receptor (PPAR) antagonists in different tumor models, being these compounds able to perturb metabolism and viability in cancer cells. In this work, the identification of a novel PPAR antagonist, showing inhibitory activity on PPARα and a weaker antagonism on PPARγ, is described. The activity of this compound and of a series of chemical analogues was investigated in selected tumor cell lines, expressing both PPARα and PPARγ. Data obtained show a dose-dependent cytotoxic effect of the novel PPAR antagonist in colorectal and pancreatic cancer models.

Keywords: CPT1A expression; PPAR antagonist; antitumor agents; cytotoxicity; sulfonamides.

Publication types

  • Letter

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Humans
  • PPAR alpha / antagonists & inhibitors*
  • PPAR alpha / metabolism
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antineoplastic Agents
  • PPAR alpha
  • PPAR gamma
  • Sulfonamides