Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer

Diana Rita Szabó, Kornélia Baghy, Peter M. Szabó, Adrienn Zsippai, István Marczell, Zoltán Nagy, Vivien Varga, Katalin Éder, Sára Tóth, Edit I. Buzás, András Falus, Ilona Kovalszky, Attila Patócs, Károly Rácz, Peter Igaz

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18 Citations (Scopus)

Abstract

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentrationand time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.

Original languageEnglish
Pages (from-to)917-932
Number of pages16
JournalCellular and Molecular Life Sciences
Volume71
Issue number5
DOIs
Publication statusPublished - Mar 1 2014

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Keywords

  • 9-Cis retinoic acid
  • Adrenocortical cancer
  • Hormone production
  • Microarray
  • Tumor growth
  • Xenograft

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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