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.
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Authors | V Giandomenico, G Vaccari, G Fiorucci, Z Percario, S Vannuchi, P Matarrese, W Malorni, G Romeo, G R Affabris |
Journal | European cytokine network
(Eur Cytokine Netw)
Vol. 9
Issue 4
Pg. 619-31
(Dec 1998)
ISSN: 1148-5493 [Print] France |
PMID | 9889406
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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-2
- Interferon-alpha
- Phosphoproteins
- RNA, Messenger
- Recombinant Proteins
- Tretinoin
- Interferon-beta
- Cyclin-Dependent Kinases
- 2',5'-Oligoadenylate Synthetase
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Topics |
- 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-2
- 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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