Suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in pituitary adenoma cells.
Pituitary adenomas, which account for 15-20% of intracranial tumors, are associated with significant morbidity and mortality, due in part, to hormone hypersecretion and mass effects following increased proliferation. Radiotherapy and surgery remain frontline treatment options; however, adverse side effects and surgical limitations to treat invasive tumors necessitate the need for novel therapeutic targets. This study tested the efficacy of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) in GH3, and MMQ pituitary adenoma cells. Clinically achievable concentrations of SAHA (500 nM-4 microM) induced growth arrest and increased cell death in GH3 pituitary adenoma cells. Further investigation into the mechanism of cell death revealed an increase in PARP cleavage and procaspase-3 activation, consistent with apoptotic cell death. SAHA also attenuated the expression of anti-apoptotic IAP (XIAP, survivin) and Bcl-2 family proteins (Bcl-2, Bcl-xL), but did not alter Bax expression. Together, these findings support a possible utility for SAHA alone or in combination with radiation for the treatment of pituitary adenoma.
Sangeetha
S R
SR
Department of Neurosurgery, Medical College of Georgia, Augusta, GA 30809, USA.
Singh
Nagendra
N
Vender
John R
JR
Dhandapani
Krishnan M
KM
D000236:Adenoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases