Angiogenesis

, Volume 16, Issue 1, pp 59–69 | Cite as

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

  • Chi Chiu Wang
  • Hui Xu
  • Gene Chi Wai Man
  • Tao Zhang
  • Kai On Chu
  • Ching Yan Chu
  • Jimmy Tin Yan Cheng
  • Gang Li
  • Yi Xin He
  • Ling Qin
  • Tat San Lau
  • Joseph Kwong
  • Tak Hang Chan
Original Paper

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 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Chi Chiu Wang
    • 1
    • 2
    • 3
  • Hui Xu
    • 1
  • Gene Chi Wai Man
    • 1
  • Tao Zhang
    • 1
  • Kai On Chu
    • 1
    • 4
  • Ching Yan Chu
    • 1
  • Jimmy Tin Yan Cheng
    • 5
  • Gang Li
    • 5
    • 6
  • Yi Xin He
    • 6
  • Ling Qin
    • 6
  • Tat San Lau
    • 1
  • Joseph Kwong
    • 1
  • Tak Hang Chan
    • 7
    • 8
  1. 1.Department of Obstetrics and GynaecologyThe Chinese University of Hong KongShatinHong Kong
  2. 2.Reproduction, Development and Endocrinology, School of Biomedical SciencesThe Chinese University of Hong KongShatinHong Kong
  3. 3.Regenerative Medicine, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongShatinHong Kong
  4. 4.Department of Ophthalmology and Visual SciencesThe Chinese University of Hong KongKowloonHong Kong
  5. 5.Stem Cells and Regeneration Program, School of Biomedical Sciences and Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongShatinHong Kong
  6. 6.Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongShatinHong Kong
  7. 7.Department of ChemistryMcGill UniversityMontrealCanada
  8. 8.Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHung HomHong Kong

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