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.

2‐methoxyestradiol impacts on amino acids‐mediated metabolic reprogramming in osteosarcoma cells by its interaction with NMDA receptor

“…Herein, we have observed anticancer effects of high concentrations of glycine and D‐serine (from 2 mM up to 532 mM) toward osteosarcoma 143B cells. Indeed, in correlation with our studies, glycine was shown to possess antiangiogenic effect on wound healing, induced liver tumors, melanoma, and mammary cancer in vivo (Bruns et al, , ). Moreover, in vivo experiments demonstrated reduction of growth rate and final volume of colorectal tumors after treatment with 1 mM glycine (Bruns et al, , ).…”

“…Indeed, in correlation with our studies, glycine was shown to possess antiangiogenic effect on wound healing, induced liver tumors, melanoma, and mammary cancer in vivo (Bruns et al, , ). Moreover, in vivo experiments demonstrated reduction of growth rate and final volume of colorectal tumors after treatment with 1 mM glycine (Bruns et al, , ). These observations provide further support that glycine might be a useful antiangiogenic and antitumor agent (Bruns et al, , ).…”

“…To the next studies we chose representative concentration of glycine and D‐serine equaled to 1 mM. Addition of 1 mM glycine and D‐serine is commonly used in vivo and in vitro studies in order to mimic physiological relevant concentration of these amino acids (Bruns et al, , ; Katsuki et al, ; Turecký, Líska, & Pechán, ; Sikka et al, ).…”

“…Moreover, in vivo experiments demonstrated reduction of growth rate and final volume of colorectal tumors after treatment with 1 mM glycine (Bruns et al, , ). These observations provide further support that glycine might be a useful antiangiogenic and antitumor agent (Bruns et al, , ). Importantly, glycine decreased the vascular endothelial growth factor and proliferation of endothelial cells.…”

Glycine Protects the Liver from Reperfusion Injury following Pneumoperitoneum

“…In recently published studies, glycine has been shown to prevent KC-dependent liver injury in chemotherapy models and inhibit angiogenesis in hepatocellular carcinoma and colorectal cancer [16][17][18]. Thus, we hypothesized that preconditioning with glycine before pneumoperitoneum prevents the activation of KCs and related phenomena, like disturbances in the hepatic microcirculation after pneumoperitoneum.…”