Dietary glycine inhibits angiogenesis during wound healing and tumor growth.
In this study we investigated the effects of glycine on angiogenesis during embryogenesis, wound healing and tumor growth. In chorioallantoic membrane (CAM) assay, glycine (100 microM) inhibited angiogenesis by more than 50%. We studied dietary glycine's effect on fibrin induced wound healing response in a novel (Fibrin Z-chamber) assay. Fibrin within the chamber triggers the healing cascade leading to formation of granulation tissue (GT) rich in blood vessels and stroma. GT was reduced by more than 30% (p < 0.0001) in dietary Glycine groups as compared to control. We found that microvessel density dropped significantly (15%, p < 0.0003) with dietary glycine whereas the other components of GT were unaffected. We evaluated tumor growth delay utilizing Tumor Z-Chamber (fibrin with R3230 mammary adenocarcinoma cells) since tumors take advantage of angiogenesis and matrix formation. We observed that tumor growth decreased by 15% (p < 0.03) and tumor microvessel density dropped by 20% (p < 0.03) with dietary glycine compared to controls. We found that iNOS protein levels were decreased significantly in both GT (24%-57%) and tumor tissue (19-75%). In conclusion, we found that dietary glycine is a potent anti-angiogenic agent that can reduce wound healing and tumor growth through reduction of iNOS expression.
Amin
Khalid
K
Drug Efficacy Organization, Biopharmaceutical Division, SRI International, Menlo Park, California, USA.
Li
Jie
J
Chao
Wan Ru
WR
Dewhirst
Mark W
MW
Haroon
Zishan A
ZA
D000482:Allantois / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002823:Chorion / Q000737:chemistry / Q000378:metabolism; D004032:Diet; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005782:Gels; D005998:Glycine / Q000008:administration & dosage*; D006097:Granulation Tissue / Q000201:enzymology / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011916:Rats, Inbred F344; D014945:Wound Healing / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D005782:Gels; D005337:Fibrin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005998:Glycine