Beta Carotene as a Chemopreventative英文资料.pdfVIP

Beta Carotene as a Chemopreventative Carcinogenesis. 2008 Nov;29(11):2153-61. Epub 2008 Jul 16. The sensitivity to beta-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells. Palozza P, Sestito R, Picci N, Lanza P, Monego G, Ranelletti FO. Institute of General Pathology, Catholic University School of Medicine, Largo F. Vito 1, Rome 00168, Italy. p.palozza@rm.unicatt.it 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 accompanie