Carcinogenesis Advance Access published online on July 16, 2008
Carcinogenesis, doi:10.1093/carcin/bgn018
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The sensitivity to β-Carotene Growth-Inhibitory and Pro-apoptotic Effects is Regulated by Caveolin-1 Expression in Human Colon and Prostate Cancer Cells
a Institutes of General Pathology, Catholic University School of Medicine, Rome
b Department of Pharmaceutical Sciences, University of Calabria, Arcavacata of Rende, Cosenza
c Institute of Pathology, Catholic University School of Medicine, Rome; Italy
d Institute of Anatomy, Catholic University School of Medicine, Rome; Italy
e Institute of Histology, Catholic University School of Medicine, Rome; Italy
1 To whom correspondence should be addressed: Dr. Paola Palozza, Institute of General Pathology, Catholic University School of Medicine, L. Go F. Vito, 1 00168 Rome (Italy). Phone: +39-06-3016619; Fax: +39-06-3386446. E-mail: p.palozza{at}rm.unicatt.it
Although several mechanisms have been proposed to explain the putative role of β-carotene in cancer, no studies have investigated a possible influence of β-carotene on caveolin-1 (cav-1) pathway, an important intracellular signalling 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 β-carotene (0.5-30 µM) for different periods of time (3-72 h) and the effects on cell growth were investigated. The results of this study show that: a) β-carotene acted as a growth-inhibitory agent in cav-1-positive cells, but not in cav-1-negative cells; b) in cav-1-positive cells, the carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of β-catenin and c-myc and the activity of caspases-3, -7, -8, -9; when the carotenoid was removed from culture medium, a progressive increase in cell growth was observed with respect to β-carotene-treated cells; c) the transfection of cav-1 in cav-1-negative cells increased cell sensitivity to β-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 β-catenin expression. Silencing of c-Myc attenuated β-carotene-induced apoptosis and β-catenin expression. All together, these data suggest that the modulation of cav-1 pathway by β-carotene could be a novel mechanism by which the carotenoid acts as a potent growth-inhibitory agent in cancer cells.
Received June 4, 2007; revised December 21, 2007; accepted January 11, 2008.