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Distinct molecular targets of proegcg from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(proegcg)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral proegcg can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and proegcg,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-proegcg inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that proegcg has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets proegcg EGCG Angiogenesis Treatment Endometriosis

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