ZR-75-1 human breast cancer cells: expression of inducible nitric oxide synthase and effect of tamoxifen and phorbol ester on nitric oxide production

The existence of the l-arginine-nitric oxide pathway was investigated in ZR-75-1 human breast cancer cells. The presence of inducible nitric oxide synthase in these cells was confirmed by staining with an anti-iNOS antibody. ZR-75-1 cells spontaneously produced nitric oxide (NO) and this production could be significantly (P<0.001) enhanced by l-arginine (0.01–10 mM) and was inhibited by l-NAME (2 mM). Stimulating the cells with phorbol 12-myristate 13-acetate (PMA) (200–1000 nM) resulted in a significant (P<0.001) increase in NO2− secreted into the medium. Although treatment of the same cells with tamoxifen (10−10–10−6 M) had no effect on NO production, tamoxifen was able to significantly (P<0.001) downregulate PMA-enhanced nitrite production. Our results suggest that tamoxifen could play a role in the biology of nitric oxide in breast tumours.