title: Phloroglucinol suppresses metastatic ability of breast cancer cells by inhibition of epithelial-mesenchymal cell transition.
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.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.
authors.forename: Rae-Kwon
authors.initials: RK
authors.lastname: Kim
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.forename: Ki-Chun
authors.initials: KC
authors.lastname: Yoo
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Cui
authors.forename: Eunji
authors.initials: E
authors.lastname: Hwang
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ju-Seop
authors.initials: JS
authors.lastname: Kang
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Young Yiul
authors.initials: YY
authors.lastname: Lee
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D020935:MAP Kinase Signaling System; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010696:Phloroglucinol / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010696:Phloroglucinol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: SLUG; basal type breast cancer cells; cancer metastasis; epithelial-mesenchymal transition; phloroglucinol