3,5,4'-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial-mesenchymal transition.

doi:10.1016/j.taap.2013.07.019

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 期刊論文 > Item 310902500/10999

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10999

Title:	3,5,4'-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial-mesenchymal transition.
Authors:	Tsai, JH Hsu, LS Lin, CL Hong, HM Pan, MH Way, TD Chen, WJ
Contributors:	中山醫學大學
Keywords:	3,5,4′-Trimethoxystilbene (MR-3);E-cadherin;Epithelial–mesenchymal transition (EMT);Glycogen synthase kinase (GSK)-3β;β-Catenin
Date:	2013
Issue Date:	2015-07-02T09:33:44Z (UTC)
ISSN:	0041-008X
Abstract:	The molecular basis of epithelial-mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4'-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10999 http://dx.doi.org/10.1016/j.taap.2013.07.019
Relation:	Toxicol Appl Pharmacol. 2013 Nov 1;272(3):746-56.
Appears in Collections:	[生化微生物免疫研究所] 期刊論文

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