title: Cooperation of histone deacetylase inhibitors SAHA and valproic acid in promoting sodium/iodide symporter expression and function in rat Leydig testicular carcinoma cells.
abstract: The presence of the sodium/iodide symporter (NIS) is the prerequisite for the use of the radioiodine in the treatment of thyroid cancer. Thus, stimulators of NIS expression and function are currently investigated in cellular models of various human malignancies, also including extrathyroid cancers. In this study, we analyzed the effects of the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), on NIS expression and function in rat Leydig testicular carcinoma cells (LC540). LC540 cells were exposed to SAHA 3 μM and VPA 3 mM (alone and in combination), and cell viability evaluated by MTT assay and cell counting, NIS mRNA and protein levels by using, respectively, real-time RT-PCR and western blotting. NIS function was evaluated by iodide uptake assay. We found that both HDACi were able to stimulate the transcription of NIS gene, but not its protein expression, while the association of SAHA and VPA increased both NIS transcript and protein levels, resulting in significant sixfold enhancement of radioiodine uptake capacity of LC540 cells. These data demonstrate the presence of an epigenetic control of NIS expression in Leydig tumor cells, suggesting the possibility to use the combination of these two HDACi for a radioiodine-based treatment of these malignancies.
authors: Department of Health Sciences, University of Catanzaro 'Magna Graecia', Viale Europa, loc. Germaneto, 88100, Catanzaro, Italy.
authors: V
authors: V
authors: Maggisano
authors: C
authors: C
authors: Puppin
authors: M
authors: M
authors: Celano
authors: M
authors: M
authors: D'Agostino
authors: M
authors: M
authors: Sponziello
authors: S
authors: S
authors: Micali
authors: M
authors: M
authors: Navarra
authors: G
authors: G
authors: Damante
authors: S
authors: S
authors: Filetti
authors: D
authors: D
authors: Russo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007984:Leydig Cell Tumor / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D051381:Rats; D027981:Symporters / Q000235:genetics* / Q000502:physiology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014635:Valproic Acid / Q000494:pharmacology*; D000077337:Vorinostat; D000099209:Sodium-Iodide Symporters
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D027981:Symporters; D014635:Valproic Acid; D000077337:Vorinostat; D000099209:Sodium-Iodide Symporters
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