Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA/MMP Expression through the FAK to ERK Pathways

Int J Med Sci. 2018 Jan 1;15(2):115-123. doi: 10.7150/ijms.22293. eCollection 2018.

Abstract

Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate future clinical trials of lung adenocarcinoma chemotherapy to confirm the promising results.

Keywords: Cinnamomum cassia.; ERK; FAK; lung cancer; metastasis.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cinnamomum aromaticum / chemistry*
  • Collagen
  • Focal Adhesion Kinase 1 / metabolism
  • Gelatin
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 2
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Urokinase-Type Plasminogen Activator / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • RHOA protein, human
  • Gelatin
  • Collagen
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Urokinase-Type Plasminogen Activator
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • rhoA GTP-Binding Protein