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

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Parthenolide reduces cell proliferation and prostaglandin estradiol synthesis in human endometriotic stromal cells and inhibits development of endometriosis in the murine model 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. Fertility and Sterility Volume 100, Issue 4, Pages 1170-1178 (October 2013) DOI: 10.1016/j.fertnstert.2013.06.028 Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Parthenolide repressed TNF-α (1 ng/mL)-induced IL-8 expression, COX-2/PGE2 expression, and DNA synthesis in human ESCs. The levels of (A) IL-8 and (C) COX-2 mRNA were assessed by real-time RT-PCR. Results are expressed as a percentage of control values. The concentration of (B) IL-8 protein and (D) PGE2 were measured by ELISA. (E) DNA synthesis after adding TNF-α was assessed by BrdU-ELISA. ∗P<.05; ∗∗P<.01 vs. control. Fertility and Sterility 2013 100, 1170-1178DOI: (10.1016/j.fertnstert.2013.06.028) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Effect of parthenolide on (A) TNF-α–induced phosphorylation of signal transduction (IκB, JNK, p38MAPK, ERK1/2, and Akt) or (B) translocation of intranuclear p65 in ESCs was evaluated by Western blot analysis or NF-κB transcription factor assay, respectively. Bars represent the average ± SE. ∗P<.05, ∗∗P<.01. Fertility and Sterility 2013 100, 1170-1178DOI: (10.1016/j.fertnstert.2013.06.028) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Cystic lesion in the mouse endometriosis model. (A) An endometriosis-like lesion developed in the murine abdominal cavity. (B) Representative of a large excised lesion. (C, D) Hematoxylin and eosin staining of lesion. Original magnification, ×40 in C, ×400 in D. Fertility and Sterility 2013 100, 1170-1178DOI: (10.1016/j.fertnstert.2013.06.028) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 4 Effect of parthenolide on murine endometriosis-like lesions. (A) Total number, (B) weight, (C) surface area of lesions, and (D) rate of Ki67-positive staining in epithelial cells of cysts were assessed. (E) Expression level of inflammation-associated genes was evaluated by real-time RT-PCR. ∗P<.05; ∗∗P<.01 vs. control. Fertility and Sterility 2013 100, 1170-1178DOI: (10.1016/j.fertnstert.2013.06.028) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions