The sensitivity to beta-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells.
Carcinogenesis
; 29(11): 2153-61, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-18635524
ABSTRACT
Although several mechanisms have been proposed to explain the putative role of beta-carotene in cancer, no studies have investigated a possible influence of beta-carotene on caveolin-1 (cav-1) pathway, an important intracellular signaling deregulated in cancer. Here, different human colon and prostate cancer cell lines, expressing (HCT-116, PC-3 cells) or not (Caco-2, LNCaP cells) cav-1, were treated with varying concentrations of beta-carotene (0.5-30 muM) for different periods of time (3-72 h) and the effects on cell growth were investigated. The results of this study show that (i) beta-carotene acted as a growth-inhibitory agent in cav-1-positive cells, but not in cav-1-negative cells; (ii) in cav-1-positive cells, the carotenoid downregulated in a dose- and time-dependent manner the expression of cav-1 protein and messenger RNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8 and -9; when the carotenoid was removed from culture medium, a progressive increase in cell growth was observed with respect to beta-carotene-treated cells and (iii) the transfection of cav-1 in cav-1-negative cells increased cell sensitivity to beta-carotene by inducing apoptosis. This effect was accompanied by a reduction of both cav-1 and AKT phosphorylation and by an increase of c-myc and beta-catenin expression. Silencing of c-Myc attenuated beta-carotene-induced apoptosis and beta-catenin expression. All together, these data suggest that the modulation of cav-1 pathway by beta-carotene could be a novel mechanism by which the carotenoid acts as a potent growth-inhibitory agent in cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Divisão Celular
/
Apoptose
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Neoplasias do Colo
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Beta Caroteno
/
Caveolina 1
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália