Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R: a microarray study

• Published in: Pharmacogenomics Vol. 13; no. 12; pp. 1351 - 1361
• Main Authors: Zsippai, Adrienn, Szabó, Diana Rita, Tömböl, Zsófia, Szabó, Peter M, Éder, Katalin, Pállinger, Éva, Gaillard, Rolf C, Patócs, Attila, Tóth, Sára, Falus, András, Rácz, Károly, Igaz, Peter
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.09.2012
• Subjects: Adrenal Cortex - drug effects; Adrenal Cortex Neoplasms - drug therapy; Adrenal Cortex Neoplasms - genetics; adrenocortical cancer; Analysis; Antineoplastic Agents, Hormonal - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Gene expression; Gene Expression - drug effects; Gene Expression - genetics; Health aspects; Hormones - genetics; Humans; microarray; Microarray Analysis - methods; Mitotane; Mitotane - pharmacology; RNA, Messenger - genetics; steroid biosynthesis; Hungary; Switzerland
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.12.116

The adrenolytic agent mitotane is widely used in the treatment of adrenocortical cancer; however, its mechanism of action is poorly elucidated. We have studied mitotane-induced mRNA expression changes in the NCI-H295R adrenocortical cancer cell line. Cell viability and hormone assays were used to select the optimal mitotane concentration effectively inhibiting hormone secretion without affecting cell viability. RNA isolated from cultures treated for 48 and 72 h was subjected to Agilent 4×44K microarray platforms. Microarray results were validated by quantitative reverse-transcription PCR. Altogether, 117 significantly differentially expressed genes were detected at 48 h and 72 h (p < 0.05) in mitotane-treated samples relative to controls. Three significantly underexpressed genes involved in steroid hormone biosynthesis ( , and ) and four significantly overexpressed genes ( , , and ) have been validated. Gene-expression changes might be involved in the adrenal action of mitotane and in the inhibition of hormone secretion. Original submitted 20 January 2012; Revision submitted 17 May 2012