Parthenolide reduces cell proliferation and prostaglandin estradiol synthesis in human endometriotic stromal cells and inhibits development of endometriosis in the murine model
2013
Takai, Eri | Taniguchi, Fuminori | Nakamura, Kazuomi | Uegaki, Takashi | Iwabe, Tomio | Harada, Tasuku
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)-α. Interleukin 8 (IL-8) and COX-2 gene expressions were evaluated by real-time reverse transcription–polymerase chain reaction. Interleukin-8 protein, prostaglandin E₂ (PGE₂) 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-α–induced IL-8 gene and protein expression in ESCs were diminished. Tumor necrosis factor α–induced COX-2 expression and PGE₂ synthesis were also inhibited. Adding parthenolide repressed TNF-α–induced 5-bromo-2′-deoxyuridine incorporation and IκB 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 κB pathway.
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