title: Antiproliferative effects of tocopherols (vitamin E) on murine glioma C6 cells: homologue-specific control of PKC/ERK and cyclin signaling.
abstract: Chemoprevention strategies for brain tumors (specifically gliomas) are few and surprisingly poorly investigated. We have studied the effects of tocopherols (TOCs; vitamin E) on proliferation and death processes of murine glioma C6 cells. These vitamers showed different cell uptake and concentration- and time-dependent inhibitory effects on cell growth that were significant at the lowest concentrations tested (1-10 microM). However, the inhibitory potency of TOCs seemed to reflect at least in part their actual cell concentrations at steady state, with the order of magnitude gamma-TOC >or= alpha-TOC > delta-TOC approximately or = beta-TOC. Moreover, for extracellular concentrations >or=10 microM, TOCs also showed a significant cytotoxic effects due mainly to necrosis, while apoptosis was negligible. Gamma-TOC (the form showing preferential cell uptake and lowest unspecific cytotoxicity) was the most effective inhibitor of cell cycle progression (arrest in G0/G1 phase) leading to lowered expression of cyclin E and cyclin-dependent kinases 2 and 4 and overexpression of p27 (specific inhibitor of S-phase entering). According to these signals, activated ERK1/2 and PKC upstream and Rb phosphorylation downstream were decreased. In conclusion, within TOCs the gamma form exerts the most potent and specific control of cell cycle progression in C6 cells (cytostatic effect). This suggests a chemopreventive role of this form of vitamin E in gliomas.
authors.affiliation: Institute of Physiological Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Betti
authors.forename: Andrea
authors.initials: A
authors.lastname: Minelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Castaldo
authors.forename: Simona
authors.initials: S
authors.lastname: Magi
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Aisa
authors.forename: Marta
authors.initials: M
authors.lastname: Piroddi
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Tomaso
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D016213:Cyclins; D014810:Vitamin E; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3