Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis

OBJECTIVE: To investigate the antitumor effects of tamoxifen on pituitary tumor GH(3) cells, which lack receptors for dopamine. METHODS: GH(3) cells were treated with tamoxifen (10(-7) mol/L), bromocriptine (10(-8) mol/L), or a combination of tamoxifen and bromocriptine in serum-free media. The cell number, bromodeoxyuridine (BrdU) labeling ratio, and apoptotic ratio were assessed. Prolactin (PRL) expression was examined using immunocytochemistry and Western blot analysis. RESULTS: After tamoxifen treatment for 4 days, the cell number decreased to 53.0% of that of untreated control cells. The percentage of PRL-immunoreactive GH(3) cells decreased to 2.9%, versus 8.6% of untreated control cells, which was compatible with the results of Western blot analysis for PRL. Apoptosis increased to approximately three times that of untreated control cells at Day 2 of treatment, whereas no significant change was shown in BrdU incorporation. These effects by tamoxifen were not observed in the simultaneous treatment with 17 beta-estradiol. Bromocriptine did not change the cell number, BrdU incorporation, the apoptotic ratio, or the percentage of PRL-positive cells, and it was also shown that tamoxifen did not change the sensitivity of GH(3) cells to bromocriptine treatment. CONCLUSION: Tamoxifen, an antiestrogen, exerts its antitumor effect on GH(3) cells in two ways: by suppression of cell growth and by causing a decrease in PRL. Apoptosis seems to contribute to the inhibition of GH(3) cell growth.