Cited by 127Angiogenesis and VEGF in CancerTea Polyphenols and EffectsCancer, Hypoxia, and Metabolism

A prodrug of green tea polyphenol (–)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer

Wang, Jianzhang, Man, Gene Chi Wai, Chan, Tak Hang, Kwong, Joseph, Wang, Chi Chiu·2018·Cancer Letters

Abstract

Anti-angiogenesis effect of a prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied. Here, we investigated how the treatment with Pro-EGCG inhibited tumor angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer were established and subjected to microarray analysis after Pro-EGCG treatment. First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models through down-regulation of vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF1α) in tumor cells and chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining. Next, we investigated how HIF1α/VEGFA was down-regulated and how the reduction of CXCL12 inhibited tumor angiogenesis. We found that VEGFA secretion from endometrial cancer cells was decreased by Pro-EGCG treatment through inhibiting PI3K/AKT/mTOR/HIF1α pathway. Furthermore, the down-regulation of CXCL12 in stromal cells by Pro-EGCG treatment restricted migration and differentiation of macrophages thereby inhibited infiltration of VEGFA-expressing tumor-associated macrophages (TAMs). Taken together, we demonstrated that treatment with Pro-EGCG not only decreases cancer cell-secreted VEGFA but also inhibits TAM-secreted VEGFA in endometrial cancer. These findings demonstrate that Pro-EGCG is a novel angiogenesis inhibitor for endometrial cancer.

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Crossref · 10.1016/j.canlet.2017.09.054

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  • EGCG inhibits the initiation, promotion, and progression of different types of tumors in vitro and in vivo.

    “Numerous studies, both in vitro using various cancer cell lines and in vivo in animal models, have consistently demonstrated the ability of EGCG to inhibit the initiation, promotion, and progression of different types of tumors.141–145”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [144]

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Authors
Wang, J., Man, G. C. W., Chan, T. H., Kwong, J., & Wang, C. C.
Affiliations
  • Chinese University of Hong Kong (HK)
  • Hong Kong Polytechnic University (HK)
Corresponding author
Wang, Chi Chiu
Venue
Cancer Letters
Publisher
Elsevier BV
Published
2018-01
Volume
412
Pages
10-20
ISSN
0304-3835 (ISSN-L)
OpenAlex
W2761665465
Cited by
127
References
44
Citations by year
2026: 6 · 2025: 11 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 18 · 2020: 29 · 2019: 13 · 2018: 11
FWCI
5.92
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Letters (publishedVersion)
  • PubMed (publishedVersion)
  • PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion)
Funders
  • University of Hong Kong
  • Chinese University of Hong Kong
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
epigallocatechin gallate, green tea polyphenols, prodrugs, endometrial cancer, tumor angiogenesis, anti-angiogenic therapy, VEGF-A, HIF-1α, PI3K/AKT/mTOR pathway, CXCL12, tumor-associated macrophages, macrophage infiltration, tumor stroma, xenograft models
MeSH terms
Phosphoinositide-3 Kinase Inhibitors, Animals, Catechin, Cell Movement, Female, Humans, Macrophages, Prodrugs, Tea, Endometrial Neoplasms, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Mice, Chemokine CXCL12

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