title: Synergistic effect of retinoic acid and dehydroepiandrosterone on differentiation of human neuroblastoma cells.
abstract: Retinoic acid (RA) affects many cell types by either promoting their survival or inducing their differentiation. Dehydroepiandrosterone (DHEA), a precursor for both androgenic and estrogenic steroids and abundantly produced by brain, is known as an inhibitor of cell proliferation. Differentiation of a human neuroblastoma cell line (SK-N-BE) was evaluated measuring growth rate, motility, neurite extension and GAP-43 expression. We report that DHEA enhances the differentiating effect of RA on neuroblastoma cells via a signalling that is not RA receptor-mediated. Instead, we show a differential expression of matrix metalloproteinases: RA enhances the activity of MMP-2, whereas MMP-9 expression is up-regulated by DHEA. The concerted modulation of these proteinases may support the neurite outgrowth observed after co-treatment with the two drugs.
authors.affiliation: Dipartimento di Genetica, Biologia e Biochimica, Facolta' di Medicina e Chirurgia, Universita' di Torino, Sezione di Biochimica, Via Santena 5 bis, 10126 Turin, Italy. francesca.silvagno@unito.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Silvagno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Guarnieri
authors.forename: Anna
authors.initials: A
authors.lastname: Capizzi
authors.forename: Gian Piero
authors.initials: GP
authors.lastname: Pescarmona
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D018168:Receptors, Retinoic Acid; D003687:Dehydroepiandrosterone; D014212:Tretinoin; D020782:Matrix Metalloproteinases