title: Beta-arrestin 2 modulates resveratrol-induced apoptosis and regulation of Akt/GSK3ß pathways.
abstract: BACKGROUND
  Resveratrol is emerging as a novel anticancer agent. However, the mechanism(s) by which resveratrol exerts its effects on endometrial cancer (EC) are unknown. We previously reported that beta-arrestin 2 plays a critical role in cell apoptosis. The role of ß-arrestin 2 in resveratrol modulation of endometrial cancer cell apoptosis remains to be established.
  
  
  METHODS
  EC cells HEC1B and Ishikawa were transfected with either ß-arrestin 2 RNA interfering (RNAi) plasmid or beta-arrestin 2 full-length plasmid and control vector. The cells were then exposed to differing concentrations of resveratrol. Apoptotic cells were detected by TUNEL assay. Expression of total and phosphorylated Akt (p-Akt), total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3ß), and caspase-3 were determined by Western blot analysis. Our data demonstrate that inhibition of ß-arrestin 2 increases the number of apoptotic cells and caspase-3 activation. Additionally ß-arrestin 2 exerted an additive effect on resveratrol-reduced levels of p-Akt and p-GSK3ß. Overexpression of ß-arrestin 2 decreased the percentage of apoptosis and caspase-3 activation and attenuated resveratrol-reduced levels of p-Akt and p-GSK3ß. Taken together, our studies demonstrate for the first time that ß-arrestin 2 mediated signaling plays a critical role in resveratrol-induced apoptosis in EC cells.
  
  
  CONCLUSIONS
  Resveratrol primes EC cells to undergo apoptosis by modulating beta-arrestin 2 mediated Akt/GSK3ß signaling pathways.
  
  
  CONCLUSIONS
  These inspiring findings would provide a new molecular basis for further understanding of cell apoptotic mechanisms mediated by ß-arrestin 2 and may provide insights into a potential clinical relevance in EC.
authors.affiliation: Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China. sunxiuli918@126.com
authors.forename: Xiuli
authors.initials: X
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianliu
authors.initials: J
authors.lastname: Wang
authors.forename: Lihui
authors.initials: L
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Gregory
authors.initials: G
authors.lastname: Hanley
authors.forename: Miaoqing
authors.initials: M
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; D000972:Antineoplastic Agents, Phytogenic; D019390:Arrestins; D013267:Stilbenes; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C505407:CASP3 protein, human; D053148:Caspase 3; D000077185:Resveratrol