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Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways

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Abstract

Tumor growth depends on angiogenesis and inducing angiogenesis is one of the most important hallmarks in the cancer development. Treatment with small molecules that inhibit angiogenesis has been an effective strategy for anti-cancer therapy. Some anti-angiogenic factors are derived from traditional Chinese herbs. Usnic acid (UA), an active compound mainly found in lichens, has shown some biological and physiological activities. However, the role and mechanism of UA in tumor angiogenesis are still unknown. The aim of this study was to assess the effects of UA on tumor angiogenesis. In this study, we demonstrated that UA strongly inhibited in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and vascular endothelial growth factor-induced mouse corneal angiogenesis model. In a mouse xenograft tumor model, UA suppressed Bcap-37 breast tumor growth and angiogenesis without affecting mice body weight. In an in vitro assay, UA not only significantly inhibited endothelial cell proliferation, migration and tube formation, but also induced morphological changes and apoptosis in endothelial cells. In addition, UA inhibited Bcap-37 tumor cell proliferation. Moreover, western blot analysis of cell signaling molecules indicated that UA blocked vascular endothelial growth factor receptor (VEGFR) 2 mediated Extracellular signal-regulated protein kinases 1 and 2(ERK1/2) and AKT/P70S6K signaling pathways in endothelial cells. These results provided the first evidence of the biological function and molecular mechanism of UA in tumor angiogenesis.

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Acknowledgments

We thank all members in the laboratory of Dr.Mingyao Liu’s lab at the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University. This study was partially sponsored by the Major State Basic Research Development Program of China (2012CB910400, 2009CB918402). National Natural Science Foundation of China (30930055, 30971523, 81071807) and The Science and Technology Commission of Shanghai Municipality (11DZ2260300).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China

    Yajuan Song, Fujun Dai, Dong Zhai, Yanmin Dong, Jing Zhang, Binbin Lu, Jian Luo, Mingyao Liu & Zhengfang Yi

  2. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, 77030, USA

    Mingyao Liu

  3. Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, TX, 77030, USA

    Mingyao Liu

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  1. Yajuan Song
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  4. Yanmin Dong
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Correspondence to Zhengfang Yi.

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Song, Y., Dai, F., Zhai, D. et al. Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways. Angiogenesis 15, 421–432 (2012). https://doi.org/10.1007/s10456-012-9270-4

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