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Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells
- Yu, Shubin, Wang, Zhongyuan, Su, Zijie, Song, Jiaxing, Zhou, Liang, Sun, Qi, Liu, Shanshan, Li, Shiyue, Li, Ying, Wang, Meina, Zhang, Guo-Qiang, Zhang, Xue, Liu, Zhong-Jian, Lu, Desheng
- BMC complementary and alternative medicine 2018 v.18 no.1 pp. 59
- Orchidaceae, Western blotting, alternative medicine, antineoplastic activity, beta catenin, bioactive compounds, breast neoplasms, cell movement, cell viability, dose response, low density lipoprotein, mechanism of action, migratory behavior, neoplasm cells, pro-apoptotic proteins, quantitative polymerase chain reaction
- BACKGROUND: Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. METHODS: The inhibitory effect of gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis. The expression of Wnt target genes was analyzed using real-time PCR. Cell viability was measured with a MTT assay. The effect of gigantol on cell migration was examined using scratch wound-healing and transwell migration assays. RESULTS: Gigantol decreased the level of phosphorylated LRP6 and cytosolic β-catenin in HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic β-catenin in a dose-dependent manner, resulting in a decrease in the expression of Wnt target genes Axin2 and Survivin. We further demonstrated that gigantol suppressed the viability and migratory capacity of breast cancer cells. CONCLUSION: Gigantol is a novel inhibitor of the Wnt/β-catenin pathway. It inhibits Wnt/β-catenin signaling through downregulation of phosphorylated LRP6 and cytosolic β-catenin in breast cancer cells.