Dietary glycine decreases both tumor volume and vascularization in a combined colorectal liver metastasis and chemotherapy model

Abstract

<b><i>Rationale:</i></b> Chemotherapy (CTx) with FOLFOX is indicated prior to resection of liver metastases; however, its effect is limited due to chemoresistance and its toxicity prevents from aggressive surgery needed in some cases. Hepatoprotective glycine has been shown to have anti-tumorigenic properties in various cancers. Thus, this study was designed to evaluate the effects of glycine combined with FOLFOX on colorectal liver metastases (CRLM). <b><i>Methods:</i></b> The effect of glycine combined with 5-fluorouracil and oxaliplatin was investigated <i>in vitro</i> on colorectal cancer (CC531). Further, Wag/Rij rats with CRLM were treated with 5% dietary glycine ± FOLFOX. µCT liver scan, anti-Ki67, and anti-CD31 were compared. <b><i>Results:</i></b> Glycine alone and combined with CTx has no effect on both CC531 viability <i>in vitro</i> and tumor proliferation <i>in vivo</i>; however, glycine significantly decreased tumor volume to about 42-35% of controls <i>in vivo</i> (p<0.05) with a 60% decreased tumor microvascular density (MVD) (p=0.004). Further glycine doesn't counteract anti-tumor properties of CTx. <b><i>Conclusions:</i></b> This study nicely demonstrates that glycine inhibits the growth of CRLM and does not decrease CTx effectiveness. Underlying mechanisms most likely include a decreased tumor MVD. Clinical trials are warranted to implement non-toxic hepatoprotective glycine in novel anti-cancer strategies in humans.