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.