Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase-plasminogen activator through modulation of the Akt signaling pathway

Environ Toxicol. 2017 Feb;32(2):645-655. doi: 10.1002/tox.22266. Epub 2016 Mar 31.

Abstract

Hispolon has been reported to possess antioxidant, antiinflammatory, and antitumor activities. However, the effect of hispolon on the metastasis of nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated how the antimetastatic activity and relevant signaling pathways of hispolon affected three NPC cell lines. The results revealed that hispolon significantly reduced the migration and invasion of three NPC cells in a dose-dependent manner from 0 to 50 µM. Hispolon also significantly inhibited the activity and expression of urokinase-plasminogen activator (uPA) as well as the phosphorylation of Akt. Moreover, blocking the Akt pathway also enhanced the antimetastatic ability of hispolon in the NPC cells. In conclusion, hispolon inhibited uPA expression and NPC cell metastasis by downregulating Akt signal pathways; therefore, hispolon exerts beneficial effects in chemoprevention. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 645-655, 2017.

Keywords: hispolon; migration; nasopharyngeal carcinoma; uPA.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinoma
  • Catechols / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy
  • Neoplasm Invasiveness
  • Phosphorylation
  • Proteolysis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Antineoplastic Agents
  • Catechols
  • hispolon
  • Proto-Oncogene Proteins c-akt
  • Urokinase-Type Plasminogen Activator