Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells
Abstract 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-c...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | BMC Complementary and Alternative Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12906-018-2108-x |
| _version_ | 1828398952630714368 |
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| author | Shubin Yu Zhongyuan Wang Zijie Su Jiaxing Song Liang Zhou Qi Sun Shanshan Liu Shiyue Li Ying Li Meina Wang Guo-Qiang Zhang Xue Zhang Zhong-Jian Liu Desheng Lu |
| author_facet | Shubin Yu Zhongyuan Wang Zijie Su Jiaxing Song Liang Zhou Qi Sun Shanshan Liu Shiyue Li Ying Li Meina Wang Guo-Qiang Zhang Xue Zhang Zhong-Jian Liu Desheng Lu |
| author_sort | Shubin Yu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T09:09:42Z |
| format | Article |
| id | doaj.art-5c63eedf4d5d4852a7360ddf13f775ec |
| institution | Directory Open Access Journal |
| issn | 1472-6882 |
| language | English |
| last_indexed | 2024-12-10T09:09:42Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary and Alternative Medicine |
| spelling | doaj.art-5c63eedf4d5d4852a7360ddf13f775ec2022-12-22T01:55:03ZengBMCBMC Complementary and Alternative Medicine1472-68822018-02-011811810.1186/s12906-018-2108-xGigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cellsShubin Yu0Zhongyuan Wang1Zijie Su2Jiaxing Song3Liang Zhou4Qi Sun5Shanshan Liu6Shiyue Li7Ying Li8Meina Wang9Guo-Qiang Zhang10Xue Zhang11Zhong-Jian Liu12Desheng Lu13Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterShenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation and Research Center of ShenzhenShenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation and Research Center of ShenzhenSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversityShenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation and Research Center of ShenzhenGuangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science CenterAbstract 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.http://link.springer.com/article/10.1186/s12906-018-2108-xGigantolLRP6Wnt/β-catenin signalingBreast cancerAnticancer activity |
| spellingShingle | Shubin Yu Zhongyuan Wang Zijie Su Jiaxing Song Liang Zhou Qi Sun Shanshan Liu Shiyue Li Ying Li Meina Wang Guo-Qiang Zhang Xue Zhang Zhong-Jian Liu Desheng Lu Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells BMC Complementary and Alternative Medicine Gigantol LRP6 Wnt/β-catenin signaling Breast cancer Anticancer activity |
| title | Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells |
| title_full | Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells |
| title_fullStr | Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells |
| title_full_unstemmed | Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells |
| title_short | Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells |
| title_sort | gigantol inhibits wnt β catenin signaling and exhibits anticancer activity in breast cancer cells |
| topic | Gigantol LRP6 Wnt/β-catenin signaling Breast cancer Anticancer activity |
| url | http://link.springer.com/article/10.1186/s12906-018-2108-x |
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