title: Allicin inhibits lymphangiogenesis through suppressing activation of vascular endothelial growth factor (VEGF) receptor.
abstract: Allicin, the most abundant organosulfur compound in freshly crushed garlic tissues, has been shown to have various health-promoting effects, including anticancer actions. A better understanding of the effects and mechanisms of allicin on tumorigenesis could facilitate development of allicin or garlic products for cancer prevention. Here we found that allicin inhibited lymphangiogenesis, which is a critical cellular process implicated in tumor metastasis. In primary human lymphatic endothelial cells, allicin at 10 μM inhibited capillary-like tube formation and cell migration, and it suppressed phosphorylation of vascular endothelial growth factor receptor 2 and focal adhesion kinase. Using a Matrigel plug assay in mice, addition of 10 μg allicin in Matrigel plug inhibited 40-50% of vascular endothelial growth factor-C-induced infiltration of lymphatic endothelial cells and leukocytes. S-Allylmercaptoglutathione, a major cellular metabolite of allicin, had no effect on lymphangiogenic responses in lymphatic endothelial cells. Together, these results demonstrate the antilymphangiogenic effect of allicin in vitro and in vivo, suggesting a novel mechanism for the health-promoting effects of garlic compounds.
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Weicang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Zheyuan
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA; Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nimiya
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Elvira
authors.initials: E
authors.lastname: Sukamtoh
authors.affiliation: Department of Mathematics and Statistics, University of Massachusetts, Amherst, MA, USA.
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA. Electronic address: guodongzhang@umass.edu.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004220:Disulfides; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013441:Sulfinic Acids / Q000494:pharmacology*; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D004220:Disulfides; D013441:Sulfinic Acids; D042582:Vascular Endothelial Growth Factor C; C006452:allicin; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Allicin; Lymphangiogenesis; Metastasis; VEGF-C