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-2b and IFN-) 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 mRNA and protein (IFNAR-1 and IFNAR-2c subunits). Both IFN-2b and IFN-1a significantly inhibited ACC cell growth in a dose-dependent manner, but the effect of IFN-1a (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 IFN-2b (IC₅₀: 57 IU/ml, maximal inhibition: 35% in H295; IC₅₀: 221 IU/ml, maximal inhibition: 60% in SW13). While in H295 cells both IFN's 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 IFN-1a in H295 cells. In H295 cells, IFN-1a, but not IFN-2b, also strongly suppressed the IGF-II mRNA expression, an important growth factor and hallmark in ACC.

Conclusions: IFN-1a is much more potent than IFN-2b to suppress ACC cell proliferation in vitro by induction of apoptosis and cell cycle arrest. Further studies are required to evaluate the potency of IFN-1a to inhibit tumor growth in vivo.