Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells

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 mu g/ml, but showed significant cytotoxicity from 50 mu g/ml. Thus, we performed subsequent experiments with PBS at doses up to 5 mu g/ml. PES dose-dependently suppressed epithelial-mesenchymal transition by downregulating the mesenchymal markers, Snaill and N-cadherin, showing significant inhibition from 1 and 5 mu g/ml, respectively. In addition, PES significantly inhibited MMP-9 activity and LOX release induced by TNF-alpha at 5 mu g/ml. Then, we determined the effect of PBS on the expression of adhesion molecules and VE-cadherin phosphorylation. The results showed that PES effectively reduced TNF-alpha-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 PBS may serve as a therapeutic agent against cancer metastasis with minimal cytotoxicity to normal cells.