title: Resveratrol inhibited GH3 cell growth and decreased prolactin level via estrogen receptors.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin 150001, Heilongjiang Province, China. chaowang194@yahoo.com.cn
authors: Chao
authors: C
authors: Wang
authors: Zhi-qiang
authors: ZQ
authors: Hu
authors: Ming
authors: M
authors: Chu
authors: Zhi
authors: Z
authors: Wang
authors: Wei-guang
authors: WG
authors: Zhang
authors: Lai-zang
authors: LZ
authors: Wang
authors: Chen-guang
authors: CG
authors: Li
authors: Jun-sheng
authors: JS
authors: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned; D056743:Cyclin D3 / Q000096:biosynthesis; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017077:Culture Media, Conditioned; D056743:Cyclin D3; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007202:Indicators and Reagents; D011960:Receptors, Estrogen; D013267:Stilbenes; D011388:Prolactin; D000077185:Resveratrol