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 concentration- and 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.
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Authors | 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 |
Journal | Cellular and molecular life sciences : CMLS
(Cell Mol Life Sci)
Vol. 71
Issue 5
Pg. 917-32
(Mar 2014)
ISSN: 1420-9071 [Electronic] Switzerland |
PMID | 23807211
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Gonadal Steroid Hormones
- Alitretinoin
- Tretinoin
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Topics |
- Adrenal Cortex Neoplasms
(drug therapy)
- Alitretinoin
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Computational Biology
(methods)
- Gene Expression Regulation, Neoplastic
(drug effects, immunology, physiology)
- Gonadal Steroid Hormones
(metabolism)
- Humans
- Mice
- Mice, Nude
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(drug effects, physiology)
- Tretinoin
(pharmacology, therapeutic use)
- Xenograft Model Antitumor Assays
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