2. Academic Validation
  3. Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells

Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells

  • BMC Complement Altern Med. 2018 Feb 14;18(1):59. doi: 10.1186/s12906-018-2108-x.
Shubin Yu 1,  Zhongyuan Wang 1,  Zijie Su 1,  Jiaxing Song 1,  Liang Zhou 1,  Qi Sun 1,  Shanshan Liu 1,  Shiyue Li 1,  Ying Li 1,  Meina Wang 2,  Guo-Qiang Zhang 2,  Xue Zhang 3,  Zhong-Jian Liu 4 5,  Desheng Lu 6
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • 2 Shenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation and Research Center of Shenzhen, Shenzhen, 518114, China.
  • 3 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 4 Shenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation and Research Center of Shenzhen, Shenzhen, 518114, China. liuzj@sinicaorchid.org.
  • 5 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. liuzj@sinicaorchid.org.
  • 6 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, 518060, China. delu@szu.edu.cn.
PMID: 29444668 DOI: 10.1186/s12906-018-2108-x
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.

Keywords

Anticancer activity; Breast cancer; Gigantol; LRP6; Wnt/β-catenin signaling.

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