Synergistic effect of retinoic acid and dehydroepiandrosterone on differentiation of human neuroblastoma cells.
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.
Silvagno
Francesca
F
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
Guarnieri
Vincenzo
V
Capizzi
Anna
A
Pescarmona
Gian Piero
GP
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
D018168:Receptors, Retinoic Acid; D003687:Dehydroepiandrosterone; D014212:Tretinoin; D020782:Matrix Metalloproteinases