Suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in pituitary adenoma cells

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11 Citations (Scopus)

Abstract

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 μM) 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.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalEndocrine
Volume35
Issue number3
DOIs
StatePublished - Jun 1 2009

Fingerprint

Pituitary Neoplasms
Apoptosis
Cell Death
Growth
Histone Deacetylase Inhibitors
Caspase 3
Neoplasms
Radiotherapy
Therapeutics
Hormones
Radiation
Morbidity
Mortality
vorinostat
Proteins

Keywords

  • Cell cycle
  • HDAC
  • Histone
  • Pituitary adenoma
  • Prolactinoma
  • Vorinostat

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in pituitary adenoma cells",
abstract = "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 μM) 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.",
keywords = "Cell cycle, HDAC, Histone, Pituitary adenoma, Prolactinoma, Vorinostat",
author = "{Sukumari Ramesh}, Sangeetha and Nagendra Singh and Vender, {John R} and Dhandapani, {Krishnan Michael}",
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AU - Sukumari Ramesh, Sangeetha

AU - Singh, Nagendra

AU - Vender, John R

AU - Dhandapani, Krishnan Michael

PY - 2009/6/1

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N2 - 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 μM) 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.

AB - 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 μM) 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.

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KW - Prolactinoma

KW - Vorinostat

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