Bakuchiol, main component of root bark of Ulmus davidiana var. japonica, inhibits TGF-β-induced in vitro EMT and in vivo metastasis

Arch Biochem Biophys. 2021 Sep 30:709:108969. doi: 10.1016/j.abb.2021.108969. Epub 2021 Jun 18.

Abstract

Cancer is a second leading cause of death worldwide, and metastasis is the major cause of cancer-related mortality. The epithelial-mesenchymal transition (EMT), known as phenotypic change from epithelial cells to mesenchymal cells, is a crucial biological process during development. However, inappropriate activation of EMT contributes to tumor progression and promoting metastasis; therefore, inhibiting EMT is considered a promising strategy for developing drugs that can treat or prevent cancer. In the present study, we investigated the anti-cancer effect of bakuchiol (BC), a main component of Ulmus davidiana var. japonica, in human cancer cells using A549, HT29 and MCF7 cells. In MTT and colony forming assay, BC exerted cytotoxicity activity against cancer cells and inhibited proliferation of these cells. Anti-metastatic effects by BC were further confirmed by observing decreased migration and invasion in TGF-β-induced cancer cells after BC treatment. Furthermore, BC treatment resulted in increase of E-cadherin expression and decrease of Snail level in Western blotting and immunofluorescence analysis, supporting its anti-metastatic activity. In addition, BC inhibited lung metastasis of tail vein injected human cancer cells in animal model. These findings suggest that BC inhibits migration and invasion of cancers by suppressing EMT and in vivo metastasis, thereby may be a potential therapeutic agent for treating cancers.

Keywords: Bakuchiol; E-cadherin; Epithelial-to-mesenchymal transition; Metastasis animal model; Root bark of Ulmus davidiana var Japonica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis / drug therapy*
  • Neoplasms / drug therapy*
  • Phenols / therapeutic use*
  • Plant Bark / chemistry
  • Plant Extracts / therapeutic use
  • Plant Roots / chemistry
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism
  • Ulmus / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Cadherins
  • Cdh1 protein, mouse
  • Phenols
  • Plant Extracts
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta
  • bakuchiol