1. 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.
- Author
-
Giandomenico V, Vaccari G, Fiorucci G, Percario Z, Vannuchi S, Matarrese P, Malorni W, Romeo G, and Affabris GR
- Subjects
- 2',5'-Oligoadenylate Synthetase genetics, Apoptosis drug effects, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Division drug effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclins biosynthesis, Cyclins genetics, DNA Fragmentation drug effects, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Drug Therapy, Combination, Enzyme Inhibitors metabolism, Female, Gene Expression drug effects, Humans, Interferon Regulatory Factor-1, Interferon alpha-2, Interferon-alpha administration & dosage, Interferon-beta administration & dosage, Phosphoproteins genetics, Phosphoproteins metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Recombinant Proteins, Tretinoin administration & dosage, Tumor Cells, Cultured, Uterine Cervical Neoplasms metabolism, Uterine Cervical Neoplasms pathology, Carcinoma, Squamous Cell therapy, Cyclin-Dependent Kinases antagonists & inhibitors, Interferon-alpha therapeutic use, Interferon-beta therapeutic use, Tretinoin therapeutic use, Uterine Cervical Neoplasms therapy
- Abstract
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.
- Published
- 1998