TY - JOUR
T1 - Anacardic acid induces caspase-independent apoptosis and radiosensitizes pituitary adenoma cells
T2 - Laboratory investigation
AU - Sukumari-Ramesh, Sangeetha
AU - Singh, Nagendra
AU - Jensen, Michael A.
AU - Dhandapani, Krishnan M.
AU - Vender, John R.
PY - 2011/6
Y1 - 2011/6
N2 - Object. Pituitary adenomas, which are common intracranial tumors, are associated with significant patient morbidity due to hormone secretion or mass effect or as a complication of therapy. Epigenetic regulation has emerged as an important component of malignant tumor pathogenesis, although the contribution in the progression of benign pituitary tumors remains largely unexplored. The present study evaluates the effect of anacardic acid (6-pentadecyl salicylic acid), a natural histone acetyltransferase inhibitor, on pituitary adenoma cells. Methods. The concentration- and time-dependent effects of anacardic acid on the viability of GH3 and MMQ pituitary adenoma cells were determined by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle phase distribution, protein expression, and percentage of apoptotic cells were assessed by flow cytometry and Western blotting. Colony forming assays were used to study the radiosensitizing effect of anacardic acid. Results. The present study identifies a novel antiproliferative and cytotoxic effect of anacardic acid on pituitary adenoma cells. These effects were associated with an increase in poly([adenosine diphosphate]-ribose) polymerase cleavage, sub-G1 arrest, and annexin V staining, consistent with apoptotic cell death; however, the pancaspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-(O-methyl)- fluoromethylketone failed to reverse anacardic acid-induced cell death, suggesting a possible nonclassical apoptotic mechanism. Anacardic acid also reduced the expression of survivin and X-linked inhibitor of apoptosis protein, antiapoptotic proteins associated with cellular survival and radioresistance, and radiosensitized pituitary adenoma cells. Conclusions. These findings warrant further exploration of anacardic acid as a single agent or as an adjunct to radiation therapy for the treatment of pituitary tumors.
AB - Object. Pituitary adenomas, which are common intracranial tumors, are associated with significant patient morbidity due to hormone secretion or mass effect or as a complication of therapy. Epigenetic regulation has emerged as an important component of malignant tumor pathogenesis, although the contribution in the progression of benign pituitary tumors remains largely unexplored. The present study evaluates the effect of anacardic acid (6-pentadecyl salicylic acid), a natural histone acetyltransferase inhibitor, on pituitary adenoma cells. Methods. The concentration- and time-dependent effects of anacardic acid on the viability of GH3 and MMQ pituitary adenoma cells were determined by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle phase distribution, protein expression, and percentage of apoptotic cells were assessed by flow cytometry and Western blotting. Colony forming assays were used to study the radiosensitizing effect of anacardic acid. Results. The present study identifies a novel antiproliferative and cytotoxic effect of anacardic acid on pituitary adenoma cells. These effects were associated with an increase in poly([adenosine diphosphate]-ribose) polymerase cleavage, sub-G1 arrest, and annexin V staining, consistent with apoptotic cell death; however, the pancaspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-(O-methyl)- fluoromethylketone failed to reverse anacardic acid-induced cell death, suggesting a possible nonclassical apoptotic mechanism. Anacardic acid also reduced the expression of survivin and X-linked inhibitor of apoptosis protein, antiapoptotic proteins associated with cellular survival and radioresistance, and radiosensitized pituitary adenoma cells. Conclusions. These findings warrant further exploration of anacardic acid as a single agent or as an adjunct to radiation therapy for the treatment of pituitary tumors.
KW - Anacardic acid
KW - Cell cycle
KW - Histone acetyltransferase
KW - Histone deacetylase
KW - Pituitary tumor
KW - Radiation
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U2 - 10.3171/2010.12.JNS10588
DO - 10.3171/2010.12.JNS10588
M3 - Article
C2 - 21275565
AN - SCOPUS:79958018870
SN - 0022-3085
VL - 114
SP - 1681
EP - 1690
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 6
ER -