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Glycine inhibits angiogenesis in colorectal cancer: role of endothelial cells

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Abstract

Neo-angiogenesis is important for tumor growth. Glycine is a non-toxic amino acid with suspected anti-angiogenic effects. This study was designed to evaluate anti-angiogenic effects of glycine in colorectal cancer. Glycine was added to cultures of human and rat colorectal cancer cells (CRC), and endothelial cells (HUVEC). Glycine’s direct impact was monitored using MTT assays. Angiogenesis in HUVEC was monitored using 3D sprouting and migration assays. VEGF and CRC-conditioned media were used to stimulate angiogenesis. The glycine receptor (GlyR) was detected using Western blotting and inhibited using strychnine. The WAG-Rij/CC-531 model of metastatic CRC was used to evaluate glycine’s impact in vivo. Tumor growth and vessel density were monitored in rats fed with or without 5 % glycine for 14 days. VEGF and conditioned media significantly increased proliferation, migration, and capillary formation to up to 267 %. Glycine completely neutralized this effect and strychnine completely blunted glycine’s effect. GlyR was detected in HUVEC. Tumor volume, weight, and vessel density decreased by 35 % (p = 0.02), 34 % (p = 0.03), and 55 % (p = 0.04) in glycine-fed animals. Glycine inhibits angiogenic signaling of endothelial cells and tumor growth. Glycine would be a promising additive to standard and targeted cancer therapies.

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Acknowledgments

The authors would like to thank Nadya Phillips-Houben for language editing.

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    Authors and Affiliations

    1. Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

      Helge Bruns, Darius Kazanavicius, Daniel Schultze, Mohammed Al Saeedi, Kenia Yamanaka & Peter Schemmer

    2. Center of Abdominal Surgery, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania

      Darius Kazanavicius & Kestutis Strupas

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    1. Helge Bruns
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    Correspondence to Peter Schemmer.

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    Handling Editor: G. J. Peters.

    H. Bruns and D. Kazanavicius contributed equally to this work.

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    Bruns, H., Kazanavicius, D., Schultze, D. et al. Glycine inhibits angiogenesis in colorectal cancer: role of endothelial cells. Amino Acids 48, 2549–2558 (2016). https://doi.org/10.1007/s00726-016-2278-0

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