Suppressive Effects of Neopterin on Inducible Nitric Oxide Synthase Gene Expression in Ovarian Carcinoma Cells in vitro

In a Number of malignant diseases including ovarian carcinomas, increased serum or urine levels of neopterin serve as a valuable marker for the state of activation of the cellular immune system. Reported correlations benveen elevated neopterin concentrations and shorter survival time of the tumor host might be explained by direct biochemical actions exhibited by the pteridine compound. In the present study, we investigated the influence of neopterin on inducible nitric oxide synthase (iNOS) gene expression in two ovarian carcinoma cell lines. Qualitative and quantitative analyses of iNOS as well as measurements of nitric oxide (NO) metabolites in the cell supernatant revealed an inhibitory effect of neopterin (1000 11M) on NO generation induced by a combination ofinterferon-γ (100 U/ml), tumor necrosis factor-a (500 U/ml), and interleukin-1β (10 U/ml). Since NO is most likely involved in apoptotic cell death in ovarian carcinoma cells, it is conceivable that suppression of NO synthesis represents a biochemical mechanism mediated by neopterin that is advantageous to tumor progression and thus harmful to the host