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Updated: Jul 15, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
07:20

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Published on: May 28, 2014

Synergy between PPARgamma ligands and platinum-based drugs in cancer

Geoffrey D Girnun1, Elnaz Naseri, Scott B Vafai

  • 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Cancer Cell
|May 8, 2007
PubMed

Insights

PPARgamma agonists combined with platinum drugs show synergistic anti-cancer effects. This combination may overcome resistance to platinum-based chemotherapy by downregulating metallothioneins.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists exhibit anti-proliferative effects.
  • PPARgamma agonists as monotherapy have not shown clinical benefits in cancer treatment.
  • Metallothioneins are implicated in resistance to platinum-based chemotherapy.

Purpose of the Study:

  • To investigate the synergistic effects of PPARgamma activation combined with chemotherapy.
  • To explore the potential of combining PPARgamma agonists with platinum-based drugs for cancer therapy.

Main Methods:

  • In vitro and in vivo studies using various cancer models.
  • Combination therapy with rosiglitazone (a PPARgamma agonist) and platinum-based drugs.
  • Analysis of PPARgamma-mediated downregulation of metallothioneins.

Main Results:

  • Significant synergy observed between rosiglitazone and platinum-based drugs across multiple cancer types.
  • Combination therapy demonstrated efficacy in vitro and in preclinical tumor models.
  • PPARgamma activation led to downregulation of metallothioneins, potentially reversing platinum resistance.

Conclusions:

  • Combining PPARgamma agonists with platinum-based drugs offers a promising strategy for treating specific human cancers.
  • This combination therapy may enhance efficacy by targeting mechanisms of platinum resistance.

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