Ciglitazone, an agonist of peroxisome proliferator-activated receptor γ, exerts potentiated cytostatic/cytotoxic effects against tumor cells when combined with lovastatin

Abstract

Thiazolidinediones are ligands of PPAR-γ, a member of the nuclear receptor family. These drugs have shown promising pre-clinical activity in tumor models but clinical studies failed to confirm their beneficial effect. We have studied the in vitro antitumor effects of a combination of ciglitazone, a thiazolidinedione drug, and lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. We observed a marked synergism in several different tumor cell lines resulting from both inhibition of cell proliferation and induction of apoptosis. These results strongly suggest that combining PPAR-γ agonists with statins can produce significant antitumor effects.