Regulation of cell-cycle progression and apoptosis by beta carotene in undifferentiated and differentiated HL-60 leukemia cells: possible involvement of a redox mechanism.

Simona Serini, Federica Wolf, Gabriella Calviello, Paola Palozza, Angela Torsello, Alma Boninsegna Lucarelli, Nicola Giuseppe Maggiano, Franco Oreste Ranelletti, Valeria Covacci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

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.
Lingua originaleEnglish
pagine (da-a)593-600
Numero di pagine8
RivistaInternational Journal of Cancer
Stato di pubblicazionePubblicato - 2002

Keywords

  • apoptosis
  • beta-carotene
  • cell cycle
  • cultured cells
  • redox

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