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Green tea catechins inhibit angiogenesis through suppression of STAT3 activation

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Previous studies indicate that green tea extract may inhibit breast cancer progression by blocking angiogenesis, although the molecular mechanisms are not well defined. We demonstrate that administration of Polyphenon E (Poly E), a standardized green tea extract, inhibited MDA-MB231 breast cancer and human dermal microvascular endothelial (HMVEC) cell migration and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9). In addition, Poly E inhibited VEGF-induced neovascularization in vivo. We also demonstrate that Poly E blocked signal transducers and activators of transcription (STAT) signaling by suppressing interferon-gamma (IFN-γ)-induced gene transcription via IFN-γ-activating sequence (GAS) elements and downstream STAT3 activation by inhibiting STAT1 and STAT3 dimerization in MDA-MB231 cells. Transient expression of constitutively active STAT3 significantly reduced the inhibitory effect of Poly E on cell migration and VEGF and MMP9 expression. Taken together, these observations indicate that green tea extract inhibits angiogenesis partly through the disruption of STAT3-mediated transcription of genes, including VEGF.

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Acknowledgments

This work was supported by the generous donation of Mr. and Mrs. Gordon I. Segal (H. Leong, P. S. Mathur, G. L. Greene), Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship PDF0503835 (H. Leong.), and the Ludwig Fund for Cancer Research (G. L. Greene). We also thank Dr. Yukihiko Hara from Mitsui Norin Co. Ltd. for the supply of Poly E.

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  1. Hoyee Leong

    Present address: University HealthSystem Consortium, 2001 Spring Road, Suite 700, Oak Brook, IL, 60523, USA

Authors and Affiliations

  1. The Ben May Department for Cancer Research, The University of Chicago, GCIS W325D, 929 East 57th Street, Chicago, IL, 60637, USA

    Hoyee Leong, Priya S. Mathur & Geoffrey L. Greene

  2. The Ben May Department for Cancer Research, The University of Chicago, GCIS W330, 929 East 57th Street, Chicago, IL, 60637, USA

    Geoffrey L. Greene

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  1. Hoyee Leong
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Correspondence to Geoffrey L. Greene.

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Author contributions: H. Leong and G. L. Greene designed research, H. Leong and P. S. Mathur performed research, and H. Leong analyzed data and wrote the paper.

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Leong, H., Mathur, P.S. & Greene, G.L. Green tea catechins inhibit angiogenesis through suppression of STAT3 activation. Breast Cancer Res Treat 117, 505–515 (2009). https://doi.org/10.1007/s10549-008-0196-x

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