title: Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice.
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.
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. ccwang@cuhk.edu.hk
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Gene Chi Wai
authors.initials: GC
authors.lastname: Man
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Kai On
authors.initials: KO
authors.lastname: Chu
authors.forename: Ching Yan
authors.initials: CY
authors.lastname: Chu
authors.forename: Jimmy Tin Yan
authors.initials: JT
authors.lastname: Cheng
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Yi Xin
authors.initials: YX
authors.lastname: He
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Tat San
authors.initials: TS
authors.lastname: Lau
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwong
authors.forename: Tak Hang
authors.initials: TH
authors.lastname: Chan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D002392:Catechin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013662:Tea / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D011355:Prodrugs; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate