Cordycepin (3'-Deoxyadenosine), an Inhibitor of mRNA Polyadenylation, Suppresses Proliferation and Activates Apoptosis in Human Epithelial Endometriotic Cells in vitro.

摘要

Background/Aims: 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. Conclusion: The mRNA polyadenylation inhibitor cordycepin inhibits proliferation and survival of endometriotic cells.