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.

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.
AuthorsV Giandomenico, G Vaccari, G Fiorucci, Z Percario, S Vannuchi, P Matarrese, W Malorni, G Romeo, G R Affabris
JournalEuropean cytokine network (Eur Cytokine Netw) Vol. 9 Issue 4 Pg. 619-31 (Dec 1998) ISSN: 1148-5493 [Print] FRANCE
PMID9889406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Interferon-alpha
  • Phosphoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • Tretinoin
  • Interferon-beta
  • interferon alfa-2b
  • Cyclin-Dependent Kinases
  • 2',5'-Oligoadenylate Synthetase
  • 2',5'-Oligoadenylate Synthetase (genetics)
  • Apoptosis (drug effects)
  • Carcinoma, Squamous Cell (metabolism, pathology, therapy)
  • Cell Division (drug effects)
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases (antagonists & inhibitors)
  • Cyclins (biosynthesis, genetics)
  • DNA Fragmentation (drug effects)
  • DNA-Binding Proteins (genetics, metabolism)
  • Drug Therapy, Combination
  • Enzyme Inhibitors (metabolism)
  • Female
  • Gene Expression (drug effects)
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-alpha (administration & dosage, therapeutic use)
  • Interferon-beta (administration & dosage, therapeutic use)
  • Phosphoproteins (genetics, metabolism)
  • RNA, Messenger (genetics, metabolism)
  • Recombinant Proteins
  • Tretinoin (administration & dosage, therapeutic use)
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms (metabolism, pathology, therapy)

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