Antifibrotic properties of epigallocatechin-3-gallate in endometriosis

Abstract

study question: Is epigallocatechin-3-gallate (EGCG) treatment effective in the treatment of fibrosis in endometriosis? summary answer: EGCG appears to have antifibrotic properties in endometriosis. what is known already: Histologically, endometriosis is characterized by dense fibrous tissue surrounding the endometrial glands and stroma. However, only a few studies to date have evaluated candidate new therapies for endometriosis-associated fibrosis. study design, size, duration: For this laboratory study, samples from 55 patients (45 with and 10 without endometriosis) of reproductive age with normal menstrual cycles were analyzed.Atotal of 40 nude mice received single injection proliferative endometrial fragments from a total of 10 samples. participants/materials, setting,methods: The in vitro effects of EGC Gand N-acetyl-L-cysteine on fibrotic markers (alphasmooth muscle actin, type I collagen, connective tissue growth factor and fibronectin) with and without transforming growth factor (TGF)-b1 stimulation, as well as on cell proliferation, migration and invasion and collagen gel contraction of endometrial and endometriotic stromal cells were evaluated by real-time PCR, immunocytochemistry, cell proliferation assays, in vitro migration and invasion assays and/or collagen gel contraction assays. The in vitro effects of EGCG on mitogen-activated protein kinase (MAPK) and Smad signaling pathways in endometrial and endometriotic stromal cellswere evaluated bywestern blotting. Additionally, the effects ofEGCGtreatment on endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice. mainresults andthe role of chance: Treatment with EGCG significantly inhibited cell proliferation, migration and invasion of endometrial and endometriotic stromal cells frompatients with endometriosis. In addition,EGCGtreatment significantly decreased the TGF-b1-dependent increase in the mRNA expression of fibrotic markers in both endometriotic and endometrial stromal cells. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels were significantly attenuated at 8, 12 and 24 h after treatment with EGCG. Epigallocatechin-3-gallate also significantly inhibited TGF-b1-stimulated activation of MAPK and Smad signaling pathways in endometrial and endometriotic stromal cells. Animal experiments showed that EGCG prevented the progression of fibrosis in endometriosis. limitations, reasons for caution: The attractiveness of epigallocatechin-3-gallate as a drug candidate has been diminished by its relatively low bioavailability. However, numerous alterations to the EGCG molecule have been patented, either to improve the integrity of the native compound or to generate a more stable yet similarly efficacious molecule. Therefore,EGCGand its derivatives, analogs and prodrugs could potentially be developed into agents for the future treatment and/or prevention of endometriosis. wider implications of thefindings: Epigallocatechin-3-gallate is a potential drug candidate for the treatment and/or prevention of endometriosis. © The Author 2014.