Identification of protocatechuic acid as a novel blocker of epithelial-to-mesenchymal transition in lung tumor cells

Phytother Res. 2021 Apr;35(4):1953-1966. doi: 10.1002/ptr.6938. Epub 2020 Nov 29.

Abstract

Protocatechuic acid (PA) is widely distributed and commonly occurring natural compound that can exert antioxidant, anti-inflammatory, as well as anti-cancer effects. Epithelial-to-mesenchymal transition (EMT) is important cellular process that can control tumor invasion and metastasis. Here, we investigated whether PA can modulate the EMT process in basal and transforming growth factorβ-induced A549 and H1299 cells. We found that PA suppressed expression of mesenchymal markers (Fibronectin, Vimentin, and N-cadherin), MMP-9, MMP-2, twist, and snail but stimulated the levels of epithelial markers (E-cadherin and Occludin). In addition, PA can affect TGFβ-induced expression of both mesenchymal and epithelial markers. Moreover, PA abrogated migratory and invasive potential of tumor cells by reversing the EMT process. Furthermore, we found that PA suppressed EMT process by abrogating the activation of PI3K/Akt/mTOR signaling cascade in lung cancer cells.

MeSH terms

  • Anticarcinogenic Agents / chemistry*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Hydroxybenzoates / chemistry*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Signal Transduction
  • Transfection

Substances

  • Anticarcinogenic Agents
  • Hydroxybenzoates
  • protocatechuic acid