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Antifibrotic properties of epigallocatechin-3-gallate in endometriosis.
Hum Reprod. 2014 Aug; 29(8):1677-87.HR

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. A total 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 EGCG and N-acetyl-l-cysteine on fibrotic markers (alpha-smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin) with and without transforming growth factor (TGF)-β1 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 cells were evaluated by western blotting. Additionally, the effects of EGCG treatment on endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice.

MAIN RESULTS AND THE ROLE OF CHANCE

Treatment with EGCG significantly inhibited cell proliferation, migration and invasion of endometrial and endometriotic stromal cells from patients with endometriosis. In addition, EGCG treatment significantly decreased the TGF-β1-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-β1-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, EGCG and its derivatives, analogs and prodrugs could potentially be developed into agents for the future treatment and/or prevention of endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS

Epigallocatechin-3-gallate is a potential drug candidate for the treatment and/or prevention of endometriosis.

STUDY FUNDING/COMPETING INTERESTS

This study was supported in part by Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared.

Authors+Show Affiliations

CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, 1, Place Lucie Aubrac, 63003 Clermont-Ferrand, France Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France CNRS, ISIT UMR6284, Clermont-Ferrand, France sachikoma@aol.com.CHU Clermont-Ferrand, Service d'Anatomie et Cytologie Pathologiques, Clermont-Ferrand, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24876174

Citation

Matsuzaki, Sachiko, and Claude Darcha. "Antifibrotic Properties of Epigallocatechin-3-gallate in Endometriosis." Human Reproduction (Oxford, England), vol. 29, no. 8, 2014, pp. 1677-87.
Matsuzaki S, Darcha C. Antifibrotic properties of epigallocatechin-3-gallate in endometriosis. Hum Reprod. 2014;29(8):1677-87.
Matsuzaki, S., & Darcha, C. (2014). Antifibrotic properties of epigallocatechin-3-gallate in endometriosis. Human Reproduction (Oxford, England), 29(8), 1677-87. https://doi.org/10.1093/humrep/deu123
Matsuzaki S, Darcha C. Antifibrotic Properties of Epigallocatechin-3-gallate in Endometriosis. Hum Reprod. 2014;29(8):1677-87. PubMed PMID: 24876174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antifibrotic properties of epigallocatechin-3-gallate in endometriosis. AU - Matsuzaki,Sachiko, AU - Darcha,Claude, Y1 - 2014/05/29/ PY - 2014/5/31/entrez PY - 2014/5/31/pubmed PY - 2015/4/8/medline KW - endometriosis KW - endometrium KW - epigallocatechin-3-gallate KW - fibrosis SP - 1677 EP - 87 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 29 IS - 8 N2 - 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. A total 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 EGCG and N-acetyl-l-cysteine on fibrotic markers (alpha-smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin) with and without transforming growth factor (TGF)-β1 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 cells were evaluated by western blotting. Additionally, the effects of EGCG treatment on endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice. MAIN RESULTS AND THE ROLE OF CHANCE: Treatment with EGCG significantly inhibited cell proliferation, migration and invasion of endometrial and endometriotic stromal cells from patients with endometriosis. In addition, EGCG treatment significantly decreased the TGF-β1-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-β1-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, EGCG and its derivatives, analogs and prodrugs could potentially be developed into agents for the future treatment and/or prevention of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Epigallocatechin-3-gallate is a potential drug candidate for the treatment and/or prevention of endometriosis. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/24876174/Antifibrotic_properties_of_epigallocatechin_3_gallate_in_endometriosis_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/deu123 DB - PRIME DP - Unbound Medicine ER -