Antiproliferative effects of interleukin-1α and nitric oxide release in a human ovarian carcinoma cell line

Interleukin-1 (IL-1) exerts direct antiproliferative effects on a number of human tumor cell lines, but the mechanisms involved are still poorly understood. Nitric oxide (NO) has been shown to mediate some of the actions of IL-1. Therefore, we investigated the role played by NO in the cytostatic effects of IL-1 alpha on NIH:OVCAR-3 cells, a cell line which has been shown to possess IL-1 receptors and to respond to the cytokine with growth arrest; the involvement of NO release in the synergistic interaction between IL-1 alpha and adriamycin (ADR) observed in this cell line was also studied. 72 h exposure to concentrations of IL-1 alpha similar to its IC50 value, were found to enhance NO release. This was significantly reduced by co-incubation with 1 mM L-NAME, which however did not significantly affect the IC50 values, either for IL-1 alpha or for the combination IL-1 alpha:ADR (1:20,000). We conclude that induction of NO synthesis in IL-1 alpha-treated cells is probably a side effect originating from transcription factor activation by the cytokine, and that neither the antiproliferative effects of IL-1 alpha nor its potentiation of ADR cytotoxicity depend on NO release.