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
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Mentions: Because phloroglucinol inhibited the invasiveness of breast cancer cells in vitro, we next examined whether phloroglucinol could suppress metastasis of breast cancer in vivo. To this end, GFP-labeled metastatic MDA-MB231 cells were transplanted into mammary fat pads of NOD-scid gamma (NSG) mice and phloroglucinol were treated four times on alternate days as indicated in Figure4(a). In tumor volumes, we observed that treatment with phloroglucinol attenuated the primary tumor formation in mammary fat pads (Fig.4b). In parallel, lung metastasis was detected markedly less in phloroglucinol-treated mice than vehicle-treated one (Fig.4c). Not surprisingly, GFP was detected in the tumor tissues, indicating that the tumors had originated from GFP-labeled cancer cells (Fig.4d). When the primary tumors in fat pad were stained by mesenchymal cell marker VIM and regulator SLUG, the expression levels of those proteins were lower in mice that are treated with phloroglucinol, compared to vehicle-treated mice (Fig.4e,f). In a similar way with in vitro data, treatment with phloroglucinol decreased phosphorylation of AKT and ERK in the primary tumors of mice (Fig.4g,h). In agreement with these results, phloroglucinol-treated mice were survived longer than the control mice (Fig.4i).
Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.