title: Glycine inhibits angiogenesis in colorectal cancer: role of endothelial cells.
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.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Helge
authors.identifier: 0000-0003-1010-1043
authors.initials: H
authors.lastname: Bruns
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.|Center of Abdominal Surgery, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors.forename: Darius
authors.initials: D
authors.lastname: Kazanavicius
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schultze
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Mohammed Al
authors.initials: MA
authors.lastname: Saeedi
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Kenia
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Center of Abdominal Surgery, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors.forename: Kestutis
authors.initials: K
authors.lastname: Strupas
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. Peter.Schemmer@med.uni-heidelberg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005998:Glycine / Q000493:pharmacokinetics / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D005998:Glycine
keywords: Angiogenesis inhibitors; Colorectal neoplasia; Endothelial cells; Glycine