title: Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol.
abstract: Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was to examine in the RA and CHOL treated SH-SY5Y cells the additive impacts of estradiol (E2) and brain-derived neurotrophic factor (BDNF) on cell morphology, cell population growth, synaptic vesicle recycling and presence of neurofilaments. The above features indicate a higher level of neuronal differentiation. Our data show that treatment for 10 days in vitro (DIV) with RA alone or when combined with E2 (RE) or CHOL (RC), but not when combined with BDNF (RB), significantly (p < 0.01) inhibited the cell population growth. Synaptic vesicle recycling, induced by high-K(+) depolarization, was significantly increased in all treatments where RA was included (RE, RC, RB, RCB), and when all agents were added together (RCBE). Specifically, our results show for the first time that E2 treatment can alone increase synaptic vesicle recycling in SH-SY5Y cells. This work contributes to the understanding of the ways to improve suppression of neuroblastoma cells' population growth by inducing maturation and differentiation.
authors.affiliation: Department of Signal Processing, Tampere University of Technology, P.O. Box 553, 33101, Tampere, Finland. heidi.teppola@tut.fi.
authors.forename: Heidi
authors.initials: H
authors.lastname: Teppola
authors.affiliation: Department of Cell Biology, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Jertta-Riina
authors.initials: JR
authors.lastname: Sarkanen
authors.affiliation: Department of Physiology and Neuroscience, St. George's University School of Medicine, St. George's, Grenada, West Indies.
authors.forename: Tuula O
authors.initials: TO
authors.lastname: Jalonen
authors.affiliation: Department of Signal Processing, Tampere University of Technology, P.O. Box 553, 33101, Tampere, Finland.
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Linne
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects / Q000648:ultrastructure; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000648:ultrastructure; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004958:Estradiol; D014212:Tretinoin; D002784:Cholesterol
keywords: Brain-derived neurotrophic factor; Cholesterol; Differentiation; Estradiol; Retinoic acid; SH-SY5Y