Original Paper

Angiogenesis

, Volume 16, Issue 1, pp 59-69

Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice

  • Chi Chiu WangAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong KongReproduction, Development and Endocrinology, School of Biomedical Sciences, The Chinese University of Hong KongRegenerative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong Email author 
  • , Hui XuAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
  • , Gene Chi Wai ManAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
  • , Tao ZhangAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
  • , Kai On ChuAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong KongDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong
  • , Ching Yan ChuAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
  • , Jimmy Tin Yan ChengAffiliated withStem Cells and Regeneration Program, School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
  • , Gang LiAffiliated withStem Cells and Regeneration Program, School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, The Chinese University of Hong Kong
  • , Yi Xin HeAffiliated withDepartment of Orthopaedics and Traumatology, The Chinese University of Hong Kong
    • , Ling QinAffiliated withDepartment of Orthopaedics and Traumatology, The Chinese University of Hong Kong
    • , Tat San LauAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
    • , Joseph KwongAffiliated withDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong
    • , Tak Hang ChanAffiliated withDepartment of Chemistry, McGill UniversityDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University

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Abstract

Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS® non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio® in vivo imaging and SCANCO® Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.

Keywords

Endometriosis Anti-angiogenesis Green tea Epigallocatechin-3-gallate