Parthenolide reduces cell proliferation and prostaglandin E2 synthesis in human endometriotic stromal cells and inhibits development of endometriosis in the murine model
Parthenolide, which occurs naturally in the medical herb feverfew, significantly repressed the development of endometriosis, possibly by suppressing peritoneal inflammatory status via the nuclear factor kB pathway.
Eri Takai, M.D., Fuminori Taniguchi, M.D., Ph.D., Kazuomi Nakamura, M.Sc. Takashi Uegaki, M.D., Tomio Iwabe, M.D., Ph.D., Tasuku Harada, M.D., Ph.D.
Volume 100, Issue 4, Pages 1170-1178, October 2013
To evaluate the effects of parthenolide on human endometriotic cells and murine endometriotic lesions.
University hospital and laboratory of animal science.
Patient(s) and Animal(s):
Twenty women with ovarian endometrioma and 30 mice.
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.
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.
Parthenolide repressed the development of endometriosis by suppressing the inflammatory peritoneal environment through the nuclear factor κB pathway.