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Lycopene induces apoptosis in immortalized fibroblasts exposed to tobacco smoke condensate through arresting cell cycle and down-regulating cyclin D1, pAKT and pBad

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Abstract

There is a lot of interest in the health benefits of dietary carotenoids and on the relationship of these compounds with smoke. In particular, it is unknown if the enhanced cancer risk observed in smokers following β-carotene supplementation can be also found using other carotenoids. Here, we studied the effects of the tomato carotenoid lycopene on molecular pathways involved in cell cycle progression, apoptosis and survival in immortalized RAT-1 fibroblasts exposed to cigarette smoke condensate (TAR). Lycopene (0.5–2.0 μM) inhibited cell growth in a dose-and time-dependent manner, by arresting cell cycle progression and by promoting apoptosis in cells exposed to TAR. The arrest of cell cycle was independent of p53 and of 8-OH-dG DNA damage and related to a decreased expression of cyclin D1. Moreover, the carotenoid up-regulated apoptosis and down-regulated the phosphorylation of AKT and Bad in cells exposed to TAR. Such an effect was associated to an inhibition of TAR-induced expression of Cox-2 and hsp90, which is known to maintain AKT activity. This study suggests that lycopene, differently from β-carotene, can exert protective effects against cigarette smoke condensate.

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Authors and Affiliations

  1. Institute of General Pathology, Catholic University, Rome

    P. Palozza, A. Sheriff, S. Serini & G. Calviello

  2. Institute of Pathology, Catholic University, Rome, Italy

    N. Maggiano

  3. Institute of Histology, Catholic University, Rome, Italy

    F. O. Ranelletti

  4. Centro di Ricerche Oncologiche Giovanni XXIII, Italy

    A. Boninsegna & A. Cittadini

  5. Institute of General Pathology, Catholic University, Rome, Italy

    P. Palozza

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  1. P. Palozza
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  2. A. Sheriff
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  3. S. Serini
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  4. A. Boninsegna
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Correspondence to P. Palozza.

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Palozza, P., Sheriff, A., Serini, S. et al. Lycopene induces apoptosis in immortalized fibroblasts exposed to tobacco smoke condensate through arresting cell cycle and down-regulating cyclin D1, pAKT and pBad. Apoptosis 10, 1445–1456 (2005). https://doi.org/10.1007/s10495-005-1393-2

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