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 to elicit the release of nitric oxide (NO) from T47D breast cancer cells in vitro.


METHODS
Prospective, longitudinal, controlled in vitro experiment.


METHODS
University Medical School, United Kingdom. MATERIAL AND INTERVENTIONS: T47D breast cancer cells were stimulated by micromolar to picomolar doses of 17beta-oestradiol, or progesterone, or both, with or without inhibition of NO or tamoxifen at 24 and 48 hours.


METHODS
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) increase 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 concentrations of NO metabolites. NO production induced by hormones was completely inhibited 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 production in T47D breast cancer cells. Inhibition of NO synthesis might be a novel therapeutic approach for reducing hormone-associated angiogenesis in breast cancer.
Thamrongwittawatpong
L
L
Department of Surgical Oncology & Technology, Hammersmith Hospital, Imperial College School of Medicine, London, United Kingdom.
Sirivatanauksorn
Y
Y
Batten
J J
JJ
Williamson
R C
RC
Kakkar
A K
AK
Mathie
R T
RT
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D011374:Progesterone / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D004967:Estrogens; D013629:Tamoxifen; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011374:Progesterone