Ciglitazone, an agonist of peroxisome proliferator-activated receptor gamma, exerts potentiated cytostatic/cytotoxic effects against tumor cells when combined with lovastatin.
Thiazolidinediones are ligands of PPAR-gamma, 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-gamma agonists with statins can produce significant antitumor effects.
Mrówka
Piotr
P
Department of Immunology, Center of Biostructure Research, The Medical University of Warsaw, 02-097 Warsaw, Poland.
Glodkowska
Eliza
E
Nowis
Dominika
D
Legat
Magdalena
M
Issat
Tadeusz
T
Makowski
Marcin
M
Szokalska
Angelika
A
Janowska
Sylwia
S
Stoklosa
Tomasz
T
Jakóbisiak
Marek
M
Golab
Jakub
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D004357:Drug Synergism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists*; D045162:Thiazolidinediones / Q000494:pharmacology*
D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; C493961:Cdkn1b protein, mouse; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008148:Lovastatin; C039671:ciglitazone