Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation
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Laurent Sakka1,3, Nathalie Delétage2, Maryse Chalus1, Youssef Aissouni5, Valérie Sylvain-Vidal4, Stéphane Gobron2 and Guillaume Coll3
1Laboratoire d'Anatomie et d'Organogenèse, Laboratoire de Biophysique Sensorielle, NeuroDol, Faculté de Médecine, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France
2Neuronax SAS, Biopôle Clermont-Limagne, F-63360 Saint-Beauzire, France
3Service de Neurochirurgie, Pole RMND, CHU de Clermont-Ferrand, Hôpital Gabriel-Montpied, 63003 Clermont-Ferrand Cedex, France
4Helixio, Biopôle Clermont-Limagne, F-63360 Saint-Beauzire, France
5Laboratoire de Pharmacologie Fondamentale et Clinique de la Douleur, NeuroDol, Faculté de Médecine, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France
Laurent Sakka, email: firstname.lastname@example.org
Keywords: neuroblastoma, citalopram, escitalopram, gene modulation, MYCN
Received: October 07, 2016 Accepted: March 15, 2017 Published: April 12, 2017
Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (p<2.26 10-7), -24.1 (p<5.6 10-9) and -17.7 (p<1.2 10-7). CCNE1, AURKA, IGF2, MYCN and ERBB2 were more moderately down-regulated by both molecules. Glioma markers E2F1, DAPK1 and CCND1 were down-regulated. Citalopram displayed more powerful action with broader and distinct spectrum of action than escitalopram.
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