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

Kim RK, Suh Y, Yoo KC, Cui YH, Hwang E, Kim HJ, Kang JS, Kim MJ, Lee YY, Lee SJ - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.

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Phloroglucinol suppresses mesenchymal traits of basal type breast cancer cells through inhibition of PI3K/AKT and KRAS/RAF-1/ERK signaling pathways. (a) PI3 kinase assay and western blot analysis for phosphorylation status of AKT after treatment with phloroglucinol. (b) Activated KRAS affinity precipitation assay, RAF-1 kinase assay and western blot analysis for phosphorylation status of ERK after treatment with phloroglucinol. (c, d) Western blot analysis for SLUG after treatment with PI3K specific inhibitor LY294002 (c) or ERK inhibitor U0126 (d). β-actin was used as a loading control.
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fig03: Phloroglucinol suppresses mesenchymal traits of basal type breast cancer cells through inhibition of PI3K/AKT and KRAS/RAF-1/ERK signaling pathways. (a) PI3 kinase assay and western blot analysis for phosphorylation status of AKT after treatment with phloroglucinol. (b) Activated KRAS affinity precipitation assay, RAF-1 kinase assay and western blot analysis for phosphorylation status of ERK after treatment with phloroglucinol. (c, d) Western blot analysis for SLUG after treatment with PI3K specific inhibitor LY294002 (c) or ERK inhibitor U0126 (d). β-actin was used as a loading control.

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).


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

Kim RK, Suh Y, Yoo KC, Cui YH, Hwang E, Kim HJ, Kang JS, Kim MJ, Lee YY, Lee SJ - Cancer Sci. (2014)

Phloroglucinol suppresses mesenchymal traits of basal type breast cancer cells through inhibition of PI3K/AKT and KRAS/RAF-1/ERK signaling pathways. (a) PI3 kinase assay and western blot analysis for phosphorylation status of AKT after treatment with phloroglucinol. (b) Activated KRAS affinity precipitation assay, RAF-1 kinase assay and western blot analysis for phosphorylation status of ERK after treatment with phloroglucinol. (c, d) Western blot analysis for SLUG after treatment with PI3K specific inhibitor LY294002 (c) or ERK inhibitor U0126 (d). β-actin was used as a loading control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317783&req=5

fig03: Phloroglucinol suppresses mesenchymal traits of basal type breast cancer cells through inhibition of PI3K/AKT and KRAS/RAF-1/ERK signaling pathways. (a) PI3 kinase assay and western blot analysis for phosphorylation status of AKT after treatment with phloroglucinol. (b) Activated KRAS affinity precipitation assay, RAF-1 kinase assay and western blot analysis for phosphorylation status of ERK after treatment with phloroglucinol. (c, d) Western blot analysis for SLUG after treatment with PI3K specific inhibitor LY294002 (c) or ERK inhibitor U0126 (d). β-actin was used as a loading control.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.

Show MeSH
Related in: MedlinePlus