SCOPE: Limited in vitro data show that lycopene may be anti-angiogenic but with unclear mechanisms. Here, we employed ex vivo and in vivo assays to substantiate the anti-angiogenic action of lycopene and determined its molecular mechanisms in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: The anti-angiogenic activity of lycopene was confirmed by ex vivo rat aortic ring and in vivo chorioallantoic membrane assays. Furthermore, the in vivo matrigel plug assay in mice demonstrated that lycopene implanted s.c. at the highest dose used (400 μg/plug) completely inhibited the formation of vascular endothelial cells induced by vascular endothelial growth factor (VEGF). As expected, lycopene inhibited tube formation, invasion, and migration in HUVECs, and such actions were accompanied by reduced activities of matrix metalloproteinase-2, urokinase-type plasminogen activator, and protein expression of Rac1, and by enhancing protein expression of tissue inhibitors of metalloproteinase-2 and plasminogen activator inhibitor-1. Moreover, lycopene attenuated VEGF receptor-2 (VEGFR2)-mediated phosphorylation of extracellular signal-regulated kinase (ERK), p38, and Akt as well as protein expression of PI3K. CONCLUSION: Our data demonstrate the anti-angiogenic effect of lycopene both in vitro and in vivo. The anti-angiogenic activity of lycopene may involve inhibition of MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways.
SCOPE: Limited in vitro data show that lycopene may be anti-angiogenic but with unclear mechanisms. Here, we employed ex vivo and in vivo assays to substantiate the anti-angiogenic action of lycopene and determined its molecular mechanisms in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: The anti-angiogenic activity of lycopene was confirmed by ex vivo rat aortic ring and in vivo chorioallantoic membrane assays. Furthermore, the in vivo matrigel plug assay in mice demonstrated that lycopene implanted s.c. at the highest dose used (400 μg/plug) completely inhibited the formation of vascular endothelial cells induced by vascular endothelial growth factor (VEGF). As expected, lycopene inhibited tube formation, invasion, and migration in HUVECs, and such actions were accompanied by reduced activities of matrix metalloproteinase-2, urokinase-type plasminogen activator, and protein expression of Rac1, and by enhancing protein expression of tissue inhibitors of metalloproteinase-2 and plasminogen activator inhibitor-1. Moreover, lycopene attenuated VEGF receptor-2 (VEGFR2)-mediated phosphorylation of extracellular signal-regulated kinase (ERK), p38, and Akt as well as protein expression of PI3K. CONCLUSION: Our data demonstrate the anti-angiogenic effect of lycopene both in vitro and in vivo. The anti-angiogenic activity of lycopene may involve inhibition of MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways.
Authors: Ke Zu; Lorelei Mucci; Bernard A Rosner; Steven K Clinton; Massimo Loda; Meir J Stampfer; Edward Giovannucci Journal: J Natl Cancer Inst Date: 2014-01-24 Impact factor: 13.506
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Authors: Abbas K Samadi; Alan Bilsland; Alexandros G Georgakilas; Amedeo Amedei; Amr Amin; Anupam Bishayee; Asfar S Azmi; Bal L Lokeshwar; Brendan Grue; Carolina Panis; Chandra S Boosani; Deepak Poudyal; Diana M Stafforini; Dipita Bhakta; Elena Niccolai; Gunjan Guha; H P Vasantha Rupasinghe; Hiromasa Fujii; Kanya Honoki; Kapil Mehta; Katia Aquilano; Leroy Lowe; Lorne J Hofseth; Luigi Ricciardiello; Maria Rosa Ciriolo; Neetu Singh; Richard L Whelan; Rupesh Chaturvedi; S Salman Ashraf; H M C Shantha Kumara; Somaira Nowsheen; Sulma I Mohammed; W Nicol Keith; William G Helferich; Xujuan Yang Journal: Semin Cancer Biol Date: 2015-05-05 Impact factor: 15.707