The effect of N-G-monomethyl-L-arginine and tamoxifen on nitric oxide production in breast cancer cells stimulated by oestrogen and progesterone

Objective: To examine the capacity of oestrogen, or progesterone, or both t o elicit the release of nitric oxide (NO) from T47D breast cancer cells in vitro. Design: Prospective, longitudinal, controlled in vitro experiment. Setting: University Medical School, United Kingdom. Material and interventions: T47D breast cancer cells were stimulated by mic romolar to picomolar doses of 17 beta -oestradiol, or progesterone, or both , with or without inhibition of NO or tamoxifen at 24 and 48 hours. Main outcome measures: Concentration of NO metabolites (nitrite + nitrate) in the culture medium measured by chemiluminescence. Results: Both hormones dose-dependently increased the proliferation of T47D without toxic effects over the range 10(-12)-10(-6) M. Both stimulated NO production at 24 hours, micomolar doses producing a pronounced (2-4 fold) i ncrease in the concentration of NO metabolites in culture medium (p = 0.002 and p < 0.001 for oestradiol and progesterone, respectively). By contrast, incubation with hormones for 48 hours had little effect on the concentrati ons of NO metabolites. NO production induced by hormones was completely inh ibited by the NO synthesis inhibitor N-G-monomethyl-L-arginine (10(-5)-10(- 3) M) and by tamoxifen (10(-8)-10(-4) M) (p < 0.001 in each case). Conclusions: Oestrogen and progesterone have a role in stimulating NO produ ction in T47D breast cancer cells. Inhibition of NO synthesis might be a no vel therapeutic approach for reducing hormone-associated angiogenesis in br east cancer.