title: Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells.
abstract: The Korean prostrate spurge Euphorbia supina is abundant in polyphenols and has been used as a folk medicine in Korea against a variety of diseases. Thus, we aimed to investigate the effect of polyphenol mixtures of Korean Euphorbia supina (PES) on the invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells. Firstly, PES showed no cytotoxicity on cancer cells and endothelial cells (ECs) at the doses of 0.1-10 µg/ml, but showed significant cytotoxicity from 50 µg/ml. Thus, we performed subsequent experiments with PES at doses up to 5 µg/ml. PES dose‑dependently suppressed epithelial-mesenchymal transition by downregulating the mesenchymal markers, Snail1 and N-cadherin, showing significant inhibition from 1 and 5 µg/ml, respectively. In addition, PES significantly inhibited MMP-9 activity and LOX release induced by TNF-α at 5 µg/ml. Then, we determined the effect of PES on the expression of adhesion molecules and VE-cadherin phosphorylation. The results showed that PES effectively reduced TNF-α-mediated VCAM-1 expression but not ICAM expression both in the MDA-MB-231 cells and ECs, resulting in the reduced adhesion of MDA-MB-231 to ECs. Finally, PES effectively inhibited MDA-MB-231 cell invasion through ECs, suggesting that PES may serve as a therapeutic agent against cancer metastasis with minimal cytotoxicity to normal cells.
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Young Nak
authors.initials: YN
authors.lastname: Joo
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.affiliation: Division of Applied Life Science (BK21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of 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, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D009363:Neoplasm Proteins; D010936:Plant Extracts; D059808:Polyphenols