Resveratrol inhibited GH3 cell growth and decreased prolactin level via estrogen receptors

Aims: Pituitary prolactinoma is one of the estrogen-related tumors, some anti-estrogen compounds have suppressive effects on prolactinoma. Previous studies have suggested that resveratrol, a phytoestrogen, displays anti-estrogen and anti-tumor characteristics. Therefore, We determined whether resveratrol could inhibit the cell proliferation and decrease prolactin level in prolactinoma cell line, and identify the signaling pathways that mediate the effects of resveratrol. Main methods: Prolactinoma cell line, GH3 cells were treated with resveratrol. Changes in proliferation, cell cycle, and apoptosis were assessed. The level of prolactin was assayed by Western blot or EIA. Expression of total Rb (retinoblastoma protein), phosphorylated Rb (pRb) and cyclin D3 were measured by Western blot. The changes of estrogen receptors and their roles in the effects of resveratrol were also determined. Key findings: We report that resveratrol had a dose-dependent inhibitory effect on GH3 cell proliferation. Inhibitory effects of resveratrol persisted, even on removal of resveratrol. The growth-inhibitory effect of resveratrol was accompanied by decreased expression of cyclin D3 and pRb. In addition, resveratrol induced G0/G1 cell cycle block and apoptosis. Furthermore, resveratrol suppressed intracellular levels and release of prolactin. Finally, we show that two types of estrogen receptor were involved in the different effects of resveratrol. Significance: Taken together, we demonstrate that resveratrol could inhibit prolactinoma cell proliferation, induce cell cycle block and apoptosis, and decrease prolactin production and release, and estrogen receptors mediate its antitumor effects. And thus, these results lead us to propose developing resveratrol as a novel therapeutic agent for treatment of prolactinoma.