Parthenolide reduces cell proliferation and prostaglandin estradiol synthesis in human endometriotic stromal cells and inhibits development of endometriosis in the murine model

Objective: To evaluate the effects of parthenolide on human endometriotic cells and murine endometriotic lesions. Design: Experimental study. Setting: University hospital and laboratory of animal science. Patient(s) and Animal(s): Twenty women with ovarian endometrioma and 30 mice. Intervention(s): Ectopic endometrial tissue from the endometrioma was collected. Main Outcome Measure(s): Human endometriotic stromal cells (ESCs) were pretreated with parthenolide and exposed to tumor necrosis factor (TNF)-alpha. Interleukin 8 (IL-8) and COX-2 gene expressions were evaluated by real-time reverse transcription-polymerase chain reaction. Interleukin-8 protein, prostaglandin E-2 (PGE(2)) level, and intranuclear p65 protein concentration were determined by ELISA. Cell proliferation was assessed by 5-bromo-2'-deoxyuridine-ELISA. Phosphorylation of signaling pathways in ESCs was evaluated by Western blotting. Gene expression and proliferative activity in murine endometriosis-like lesions were assessed by real-time reverse transcription-polymerase chain reaction and Ki67 staining, respectively. Result(s): With parthenolide pretreatment, TNF-alpha-induced IL-8 gene and protein expression in ESCs were diminished. Tumor necrosis factor alpha-induced COX-2 expression and PGE2 synthesis were also inhibited. Adding parthenolide repressed TNF-alpha-induced 5-bromo-2'-deoxyuridine incorporation and I kappa B phosphorylation in ESCs. As in vivo experiments, administering parthenolide reduced the number, surface area, and weight, the level of Vegf, Il-6, Mcp-1, and Lif gene expression, and the percentage of Ki67-positive cells in murine endometriosis-like lesions. Conclusion(s): Parthenolide repressed the development of endometriosis by suppressing the inflammatory peritoneal environment through the nuclear factor kappa B pathway. (C) 2013 by American Society for Reproductive Medicine