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
  • 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. [email protected].
  • 5. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. [email protected].
  • 6. Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, 518060, China. [email protected].
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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