Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth.
CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Despite efforts to develop new therapeutic regimens for metastatic ACC, surgery remains the mainstay of treatment. Interferons are known to exert tumor-suppressive effects in several types of human cancer. DESIGN: We evaluated the tumor-suppressive effects of type I interferons (IFN)-alpha2b and IFNbeta on the H295 and SW13 human ACC cell lines. RESULTS: As determined by quantitative RT-PCR analysis and immunocytochemistry, H295 and SW13 cells expressed the active type I IFN receptor (IFNAR) mRNA and protein (IFNAR-1 and IFNAR-2c subunits). Both IFNalpha2b and IFNbeta1a significantly inhibited ACC cell growth in a dose-dependent manner, but the effect of IFNbeta1a (IC50 5 IU/ml, maximal inhibition 96% in H295; IC50 18 IU/ml, maximal inhibition 85% in SW13) was significantly more potent, compared with that of IFNalpha2b (IC50 57 IU/ml, maximal inhibition 35% in H295; IC50 221 IU/ml, maximal inhibition 60% in SW13). Whereas in H295 cells both IFNs induced apoptosis and accumulation of the cells in S phase, the antitumor mechanism in SW13 cells involved cell cycle arrest only. Inhibitors of caspase-3, caspase-8, and caspase-9 counteracted the apoptosis-inducing effect by IFNbeta1a in H295 cells. In H295 cells, IFNbeta1a, but not IFNalpha2b, also strongly suppressed the IGF-II mRNA expression, an important growth factor and hallmark in ACC. CONCLUSIONS: IFNbeta1a is much more potent than IFNalpha2b to suppress ACC cell proliferation in vitro by induction of apoptosis and cell cycle arrest. Further studies are required to evaluate the potency of IFNbeta1a to inhibit tumor growth in vivo.
|Keywords||Adrenal Cortex Neoplasms/drug therapy, Adrenocortical Carcinoma/drug therapy, Apoptosis/drug effects, Cell Cycle/drug effects, Cell Proliferation/*drug effects, Humans, Hydrocortisone/secretion, Interferon Alfa-2b/pharmacology, Interferon Type I/*pharmacology/therapeutic use, Interferon-beta/pharmacology, Receptor, Interferon alpha-beta/metabolism, Tumor Cells, Cultured|
|Persistent URL||dx.doi.org/10.1210/jc.2006-0620, hdl.handle.net/1765/14034|
|Journal||Journal of Clinical Endocrinology and Metabolism|
van Koetsveld, P.M, Vitale, G, de Herder, W.W, Feelders, R.A, van der Wansem, K, Waaijers, M, … Hofland, L.J. (2006). Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. Journal of Clinical Endocrinology and Metabolism, 91(11), 4537–4543. doi:10.1210/jc.2006-0620