title: Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA-MB-231.
abstract: Recent evidence suggests that polyphenolic compounds from plants have anti-invasion and anti-metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti-metastatic effects of pKAL on the highly metastatic MDA-MB-231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial-mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA-MB-231 cells in a dose-dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA-MB-231 cells to ECs through reducing vascular cell adhesion molecule-1 expression of MDA-MB-231 and ECs, but not intracellular adhesion molecule-1 at the concentrations where pKAL did not influence the cell viability of either MDA-MB-231 cells nor EC. Further, pKAL inhibited tumor necrosis factor-activated MDA-MB-231 breast cancer cell invasion through inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule-1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Ko
authors.affiliation: Internal Medicine, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Internal Medicine, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Radha
authors.initials: R
authors.lastname: Panchanathan
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Young Nak
authors.initials: YN
authors.lastname: Joo
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Department of Biomaterial Control (BK21 program), Graduate School, Dong-eui University, Busan, 614-052, South Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: School of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, South Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Neurosurgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.affiliation: Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, South Korea.
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.affiliation: Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, 660-701, South Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-702, South Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D031172:Artemisia annua / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D059808:Polyphenols; D019010:Vascular Cell Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Artemisia annua L; EMT; VCAM-1; breast cancer cell; endothelial cell; metastasis