Phloroglucinol suppresses metastatic ability of breast cancer cells by inhibition of epithelial-mesenchymal cell transition.
Bottom Line: 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.
Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.Show MeSH
Related in: MedlinePlus
Mentions: Because PI3K/AKT and RAS/RAF-1/ERK signaling pathways have been shown to regulate EMT in many cancer cells,11–13 we examined whether phloroglucinol shows its effect by inhibition of these pathways. To this end, we examined whether phloroglucinol could inhibit the activity of PI3K, AKT, KRAS, RAF-1 and ERK signaling components in basal type MDA-MB231 and BT549 breast cancer cells. Importantly, treatment with phloroglucinol inhibited the activity of PI3K and the phosphorylation of AKT in basal type breast cancer cells (Figs3a, S2A). Also, phloroglucinol effectively decreased the active form of KRAS that could interact with RAF-1 (Fig.3b). In parallel, treatment with phloroglucinol decreased the activity of RAF-1 and the phosphorylation of ERK (Figs3b, S2B).
Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.