Farnesol abrogates epithelial to mesenchymal transition process through regulating Akt/mTOR pathway

Pharmacol Res. 2019 Dec:150:104504. doi: 10.1016/j.phrs.2019.104504. Epub 2019 Oct 31.

Abstract

Epithelial mesenchymal transition (EMT) refers to a phenomenon through which epithelial cells develop the metastatic and invasive potential, which are closely related to carcinogenesis. Farnesol (FOH) obtained from the oils of diverse plants can exhibit significant therapeutic actions against obesity, diabetes, inflammatory conditions and cancers. Here, we evaluated the potential effects of FOH on growth and metastasis and it was observed that FOH significantly abrogated cell proliferation in lung cancer cells. Moreover, FOH inhibited cell repair movement by wound healing assay and reduced cell adhesion. It suppressed the expression of mesenchymal genes such as fibronectin, vimentin, N-cadherin, twist, and snail, and increased expression of epithelial genes such as occludin and E-cadherin. It also attenuated the migration and invasion through the inhibition of the PI3K/Akt/mTOR signaling pathway. Furthermore, FOH inhibited the tumor growth of xenograft mouse lung cancer model, and modulated the expression of mesenchymal and epithelial markers. The results suggest that FOH may block the PI3K/Akt/mTOR signaling pathway and thus exhibit anti-proliferative and anti-metastatic activity against lung cancer cells.

Keywords: Akt; EMT; Farnesol; NSCLC; TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Farnesol / pharmacology*
  • Farnesol / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice, Nude
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents
  • Farnesol
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases