RESUMEN
Resveratrol (RE), a phytoestrogen, has antiestrogenic properties. Estrogen plays a key role in the development and progression of pituitary prolactinoma. Moreover, RE is a potent cancer chemopreventive agent that inhibits the initiation, promotion and progression of carcinogenesis. The present study investigated the antitumor effects of RE on GH3 pituitary tumor cells. A concentration- and treatment duration-dependent biphasic effect of RE on the proliferation of the GH3 cells was demonstrated. After three days of treatment, RE stimulated proliferation at low concentrations and inhibited proliferation at high concentrations. However, when the treatment duration was reduced to 6 h, RE inhibited proliferation in a concentration-dependent manner. In addition, RE induced apoptosis with the activation of caspase-3 and -8, and decreased the percentage of prolactin (PRL)-immunopositive GH3 cells. Furthermore, RE suppressed expression of the PRL gene and inhibited the cell proliferation and PRL synthesis induced by 17ß-estradiol (E2). In GH3 cells, the proliferation response exhibited higher sensitivity to E2 compared with the PRL response; by contrast, the PRL response was more sensitive to RE than the proliferation response was. These results indicate that RE, an antiestrogenic compound, exerts its antitumor effect on GH3 cells through the suppression of GH3 cell growth and through the inhibition of PRL synthesis. The RE-induced cell apoptosis was shown to be caspase-dependent. Therefore, the present study provides support for the use of RE in the chemoprevention and chemotherapy of pituitary prolactinoma.