Anti-tumour Activity of CS-7017, a Selective Peroxisome Proliferator-Activated Receptor Gamma Agonist of Thiazolidinedione Class, in Human Tumour Xenografts and a Syngeneic Tumour Implant Model

Eur J Cancer. 2008 Aug;44(12):1734-43. doi: 10.1016/j.ejca.2008.04.016. Epub 2008 May 27.

Abstract

The anti-tumour activity of the novel thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARgamma) agonist CS-7017 was investigated. CS-7017 activated PPARgamma-mediated luciferase expression with an EC(50) of 0.20 nM. In addition, CS-7017 was shown to be highly selective for PPARgamma amongst other PPAR subfamilies. CS-7017 inhibited the proliferation of the human anaplastic thyroid tumour cell line DRO and the pancreatic tumour cell line AsPC-1 in vitro at concentrations as low as 10 nM. In xenograft studies, CS-7017 inhibited the growth of the human colorectal tumour cell line HT-29 in nude mice as well as DRO in nude rats in a dose-dependent manner. At the same dose, an increase in the levels of adiponectin, a surrogate marker for PPARgamma activation, was also observed. CS-7017 prolonged the survival of mice inoculated with murine colorectal tumour Colon 38 with marginal tumour growth inhibition. These preclinical results support the potential utility of CS-7017 in a clinical setting.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / metabolism
  • Mice
  • Mice, Nude
  • PPAR gamma / agonists*
  • Thiazolidinediones / metabolism
  • Thiazolidinediones / therapeutic use*
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Luciferases
  • efatutazone