title: Dieckol as a novel anti-proliferative and anti-angiogenic agent and computational anti-angiogenic activity evaluation.
abstract: In the current study it was found that dieckol isolated from edible brown algae, Ecklonia cava (EC), as potent anti-proliferative and anti-angiogenic agent. Vascular endothelial growth factor (VEGF) induced EA.hy926 cell proliferation was suppressed by dieckol treatment. Further, it showed a significant inhibition of cell migration via inhibiting the protein and gene expression levels of matrix metalloproteinases, MMP-2 and -9. The signaling cascade underlying these responses was found as the dieckol induced inhibition of mitogen-activated protein kinase (MAPK) signaling pathway molecules, ERK and p38. Docking calculations were carried out on AP-N, VEGFR-1, MMP-2, MMP-9, Akt and Erk2 proteins model. Collectively, these results demonstrate the effective anti-proliferative and anti-migratory activity of dieckol on VEGF induced EA.hy926 through MAPK molecular signaling pathways which could be effectively correlated to its potential as an anti-angiogenic candidate. Therefore, this study reveals the potential of dieckol to be used in the design of anti-angiogenic agents.
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, 1035, Boshuo Road, Jing Yue Economic Development Zone, Chanchun City, Jilin Province, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Specialized Graduate School Science and Technology Convergence, Department of Marine Bio Convergence Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Je
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea; Specialized Graduate School Science and Technology Convergence, Department of Marine Bio Convergence Science, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: sknkim@pknu.ac.kr.
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D062105:Molecular Docking Simulation; D000459:Phaeophyceae; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D001572:Benzofurans; D042461:Vascular Endothelial Growth Factor A; C503840:dieckol; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D018826:CD13 Antigens; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Anti-angiogenic agent; Dieckol; MAPK pathway; Molecular docking server; Phlorotannins