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Apoptosis and growth inhibition of squamous carcinoma cells treated with interferon-alpha, IFN-beta and retinoic acid are associated with induction of the cyclin-dependent kinase inhibitor p21. |
European Cytokine Network. Volume 9, Number 4, 619-32, December 1998, Articles originaux
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 Free Article
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Author(s) : V. Giandomenico, G. Vaccari, G. Fiorucci, Z. Percario, S. Vannuchi, P. Matarrese, W. Malorni, G. Romeo and E. Affabris |
Summary : Recent studies have revealed promising leads on the potential of interferons (IFNs) in combination with retinoids in solid tumor therapy. The role of IFN-alpha and retinoic acid (RA) in cervical cancer is currently under active study. Because preclinical and clinical data on IFN-beta in combination with retinoids show promising results against breast carcinoma, we analysed the anti-proliferative effect of human recombinant IFN-beta alone or in combination with all-trans RA on two human squamous cervical carcinoma cell (SCC) lines (ME180 and SiHa). The two cell lines differ in their sensitivity to the anti-proliferative effects of the different agents and their combination: i) both cell lines were more responsive to IFN-beta than to IFN-alpha2b; ii) combined treatment with RA increases the growth inhibitory effect of the single agents in ME180, but not in SiHa; iii) the antiproliferative effect correlates with the induction of apoptosis. We suggest as a possible mechanisms of action that interferon regulatory factor-1 (IRF-1), a transcription factor which belongs to the IFN machinery, and the cyclin-dependent kinase inhibitor (CDKi) p21 can be involved in cellular growth inhibition and in the induction of apoptosis. These results support the use of IFN-beta in further clinical investigation possibly in combination with retinoids. |
Keywords : interferon, all-trans retinoic acid, apoptosis, squamous carcinoma, CDKi p21. |
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