Phloroglucinol suppresses metastatic ability of breast cancer cells by inhibition of epithelial‐mesenchymal cell transition

Cancer Science

Rae-Kwon Kim⁴  Yongjoon Suh⁴  Ki-Chun Yoo⁴  Yan-Hong Cui⁴  Eunji Hwang⁴  Hyun-Jin Kim¹  Ju-Seop Kang¹  Min-Jung Kim³  Young Yiul Lee² 

[1] Department of Pharmacology and Clinical Pharmacology Lab, College of Medicine, Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Seoul, South Korea;Division of Hematology/Oncology, Department of Internal Medicine, Hanyang University, Seoul, South Korea;Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea;Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea

关键词: basal type breast cancer cells;    cancer metastasis;    epithelial‐mesenchymal transition;    phloroglucinol;    SLUG;   

DOI  :  10.1111/cas.12562

来源: Wiley

【 摘 要 】

Abstract

Metastasis is a challenging clinical problem and the primary cause of death in breast cancer patients. However, there is no therapeutic agent against metastasis of breast cancer cells. Here we report that phloroglucinol, a natural phlorotannin component of brown algae suppresses metastatic ability of breast cancer cells. Treatment with phloroglucinol effectively inhibited mesenchymal phenotypes of basal type breast cancer cells through downregulation of SLUG without causing a cytotoxic effect. Importantly, phloroglucinol decreased SLUG through inhibition of PI3K/AKT and RAS/RAF-1/ERK signaling. In agreement with in vitro data, phloroglucinol was also effective against in vivo metastasis of breast cancer cells, drastically suppressing their metastatic ability to lungs, and extending the survival time of mice. Collectively, our findings demonstrate a novel anticancer activity of phloroglucinol against metastasis of breast cancer cells, implicating its clinical relevance.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.