Regulation of cellular processes by PPARgamma ligands in neuroblastoma cells is modulated by the level of retinoblastoma protein expression.
Neuroblastoma is a childhood cancer, which spontaneously regresses. This has led to a search for agents that mimic this process. We show that both natural and synthetic ligands of PPARgamma (peroxisome-proliferator-activated receptor gamma) inhibit the growth of neuroblastoma cells in vitro. The degree of PPAR activation was attenuated however in the presence of the retinoblastoma protein. Addition of trichostatin A, a histone deacetylase inhibitor, abolished retinoblastoma protein repression of PPAR activity. Moreover, enhanced growth inhibition was observed when neuroblastoma cells were treated with a PPARgamma ligand and a histone deacetylase inhibitor, suggesting a combination therapy to treat neuroblastoma might prove more effective than using either agent alone.
Emmans
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Development and Cell Biology, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Rodway
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HA
Hunt
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Lillycrop
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KA
D002262:Carboxy-Lyases / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008024:Ligands; D009447:Neuroblastoma / Q000378:metabolism*; D047495:PPAR gamma / Q000737:chemistry*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
C477819:15-deoxyprostaglandin J2; D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D008024:Ligands; D047495:PPAR gamma; D016160:Retinoblastoma Protein; D045162:Thiazolidinediones; C012589:trichostatin A; D002262:Carboxy-Lyases; D015230:Prostaglandin D2; C039671:ciglitazone