Pyrrolidine Dithiocarbamate Attenuates Nuclear Factor-ĸB Activation, Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Endometriotic Epithelial Cells

Abstract

Background: The nuclear factor-ĸB (NF-ĸB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-ĸB inhibitor, in the treatment of endometriosis. Methods: The phosphorylation of IĸB, expression of nuclear p65 protein and NF-ĸB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E₂ (PGE₂) production of EECs was measured by ELISA. Results: PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IĸB phosphorylation, expression of nuclear p65 protein and NF-ĸB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE₂ synthesis. Conclusion: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.