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

Ko,Young  Shin; Lee,Won  Sup; Joo,Young  Nak; Choi,Yung  Hyun; Kim,Gon  Sup; Jung,Jin-Myung; Ryu,Chung  Ho; Shin,Sung  Chul; Kim,Hye  Jung

doi:10.3892/or.2015.4304

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

Authors:
- Young Shin Ko
- Won Sup Lee
- Young Nak Joo
- Yung Hyun Choi
- Gon Sup Kim
- Jin-Myung Jung
- Chung Ho Ryu
- Sung Chul Shin
- Hye Jung Kim
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Affiliations: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea, Department of Internal Medicine, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea, 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, School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Neurosurgery, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea, Division of Applied Life Science (BK21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
Published online on: September 22, 2015 https://doi.org/10.3892/or.2015.4304
Pages: 3035-3042

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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.

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