TY - JOUR
T1 - Regulation of cell-cycle progression and apoptosis by beta carotene in undifferentiated and differentiated HL-60 leukemia cells: possible involvement of a redox mechanism.
AU - Palozza, Paola
AU - Serini, Simona
AU - Torsello, Angela
AU - Boninsegna Lucarelli, Alma
AU - Covacci, Valeria
AU - Maggiano, Nicola Giuseppe
AU - Ranelletti, Franco Oreste
AU - Wolf Minotti, Federica
AU - Calviello, Gabriella
PY - 2002
Y1 - 2002
N2 - Although epidemiologic studies have demonstrated that a high intake of vegetables containing beta-carotene lowers the risk of cancer, recent intervention studies have revealed that beta-carotene supplementation to smokers resulted in a high incidence of lung cancer. We hypothesized that beta-carotene may act as a pro- or anticancerogenic agent by modulating pathways involved in cell growth and that such a modulation may involve a redox mechanism. To test this hypothesis, cell proliferation, apoptosis and redox status were evaluated in undifferentiated and dimethylsulfoxide-differentiated HL-60 cells exposed to beta-carotene. The carotenoid modified cell cycle progression and induced apoptosis in a dose-dependent manner. These effects were more remarkable in undifferentiated cells than in differentiated cells. In accord with these findings, in undifferentiated cells, beta-carotene was more effective in decreasing cyclin A and Bcl-2 expression and in increasing p21 and p27 expression. Neither Bcl-xL nor Bax expression were significantly modified by the carotenoid. From a mechanistic point of view, the delay in cell growth by beta-carotene was highly coincident with the increased intracellular reactive oxygen species production and oxidized glutathione content induced by the carotenoid. Moreover, alpha-tocopherol minimized the effects of beta-carotene on cell growth. These data provide evidence that beta-carotene modulates molecular pathways involved in cell cycle progression and apoptosis and support the hypothesis that a redox mechanism may be implicated. They also suggest that differentiated cells may be less susceptible to the carotenoid than highly neoplastic undifferentiated cells.
AB - Although epidemiologic studies have demonstrated that a high intake of vegetables containing beta-carotene lowers the risk of cancer, recent intervention studies have revealed that beta-carotene supplementation to smokers resulted in a high incidence of lung cancer. We hypothesized that beta-carotene may act as a pro- or anticancerogenic agent by modulating pathways involved in cell growth and that such a modulation may involve a redox mechanism. To test this hypothesis, cell proliferation, apoptosis and redox status were evaluated in undifferentiated and dimethylsulfoxide-differentiated HL-60 cells exposed to beta-carotene. The carotenoid modified cell cycle progression and induced apoptosis in a dose-dependent manner. These effects were more remarkable in undifferentiated cells than in differentiated cells. In accord with these findings, in undifferentiated cells, beta-carotene was more effective in decreasing cyclin A and Bcl-2 expression and in increasing p21 and p27 expression. Neither Bcl-xL nor Bax expression were significantly modified by the carotenoid. From a mechanistic point of view, the delay in cell growth by beta-carotene was highly coincident with the increased intracellular reactive oxygen species production and oxidized glutathione content induced by the carotenoid. Moreover, alpha-tocopherol minimized the effects of beta-carotene on cell growth. These data provide evidence that beta-carotene modulates molecular pathways involved in cell cycle progression and apoptosis and support the hypothesis that a redox mechanism may be implicated. They also suggest that differentiated cells may be less susceptible to the carotenoid than highly neoplastic undifferentiated cells.
KW - apoptosis
KW - beta-carotene
KW - cell cycle
KW - cultured cells
KW - redox
KW - apoptosis
KW - beta-carotene
KW - cell cycle
KW - cultured cells
KW - redox
UR - http://hdl.handle.net/10807/23786
M3 - Article
SN - 0020-7136
SP - 593
EP - 600
JO - International Journal of Cancer
JF - International Journal of Cancer
ER -