title: Cordycepin (3'-deoxyadenosine), an inhibitor of mRNA polyadenylation, suppresses proliferation and activates apoptosis in human epithelial endometriotic cells in vitro.
abstract: OBJECTIVE
  Endometriosis is a benign but chronic disorder associated with pelvic pain and infertility. Enhanced proliferation and reduced apoptosis susceptibility are characteristics of endometriosis. Cordycepin is a poly(A) polymerase inhibitor. It induces shortening of poly(A) tails, leading to destabilization of mRNAs and finally to proliferation inhibition and cell death in normal and tumor cells. The potential of cordycepin to block proliferation and survival of 11z human immortalized epithelial endometriotic cells was determined.
  
  
  METHODS
  11z cell cultures were treated with cordycepin. Cordycepin-induced inhibition of proliferation and alterations in protein expression and protein phosphorylation were determined by the methyl thiazolyl tetrazolium assay and immunoblot analysis, respectively.
  
  
  RESULTS
  Cordycepin induced the rapid and significant upregulation of the cell cycle progression inhibitor p21 and the downregulation of the cell cycle progression promoter cyclin D(1), finally leading to the inhibition of the proliferation of 11z human epithelial endometriotic cells. Cordycepin reduced the phosphorylation of the p38 mitogen-activated protein kinase and the retinoblastoma protein. It also activated caspase-dependent, intrinsic apoptosis, as documented by the proteolytic cleavage of the caspase-9, caspase-3 and the poly(ADP ribose) polymerase 1 precursor.
  
  
  CONCLUSIONS
  The mRNA polyadenylation inhibitor cordycepin inhibits proliferation and survival of endometriotic cells.
authors.affiliation: Department of Gynecology, University Hospital Zurich, Frauenklinikstrasse 10, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Imesch
authors.forename: René
authors.initials: R
authors.lastname: Hornung
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.forename: André
authors.initials: A
authors.lastname: Fedier
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D003839:Deoxyadenosines / Q000494:pharmacology*; D004715:Endometriosis / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D026723:Polyadenylation / Q000187:drug effects; D011062:Polynucleotide Adenylyltransferase / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D003839:Deoxyadenosines; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D011062:Polynucleotide Adenylyltransferase; C058120:cordycepin