Interferon-a (IFN-alpha) is used for biotherapy of neuroendocrine carcinomas. The interferon-lambda s (IL-28A/B and IL-29) are a novel group of interferons. In this study, we investigated the effects of the IFN-lambda s IL-28A and IL-29 on human neuroendocrine BON1 tumor cells. Similar to IFN-alpha, incubation of BON1 cells with IL-28A (10 ng/ml) and IL-29 (10 ng/ml) induced phosphorylation of STAT1, STAT2, and STAT3, significantly decreased cell numbers in a proliferation assay, and induced apoptosis as demonstrated by poly(ADP-ribose) polymerase (PARP)-cleavage, caspase-3-cleavage, and DNA-fragmentation. Stable overexpression of suppressor of cytokine signaling proteins (SOCS1 and SOCS3) completely abolished the aforementioned effects indicating that SOCS proteins act as negative regulators of IFN-lambda signaling in BON1 cells. In conclusion, the novel IFN-lambda s IL-28A and IL-29 potently induce STAT signaling and antiproliferative effects in neuroendocrine BON1 tumor cells. Thus, IFN-lambda s may hint a promising new approach in the antiproliferative therapy of neuroendocrine tumors. (c) 2006 Elsevier Inc. All rights reserved.