Journal Article

The sensitivity to β-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells

Paola Palozza, Rosanna Sestito, Nevio Picci, Paola Lanza, Giovanni Monego and Franco O. Ranelletti

in Carcinogenesis

Volume 29, issue 11, pages 2153-2161
Published in print November 2008 | ISSN: 0143-3334
Published online July 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn018
The sensitivity to β-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells

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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 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 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 (i) β-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 β-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 β-carotene-treated cells and (iii) 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.

Journal Article.  6416 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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