α-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion

Cancer Lett. 2014 May 28;347(1):129-38. doi: 10.1016/j.canlet.2014.02.003. Epub 2014 Feb 7.

Abstract

Recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of PSCs and hypoxia in pancreatic cancer aggressiveness, and examined the potential protective effect of α-mangostin on hypoxia-driven pancreatic cancer progression. Our data indicate that hypoxic PSCs exploit their oxidative stress due to hypoxia to secrete soluble factors favouring pancreatic cancer invasion. α-Mangostin suppresses hypoxia-induced PSC activation and pancreatic cancer cell invasion through the inhibition of HIF-1α stabilization and GLI1 expression. Increased generation of hypoxic ROS is responsible for HIF-1α stabilization and GLI1 upregulation. Therefore, α-mangostin may be beneficial in preventing hypoxia-induced pancreatic cancer progression.

Keywords: Hypoxia; PSC; Pancreatic cancer; ROS; α-Mangostin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia*
  • Cell Line, Tumor
  • Cells, Cultured
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neoplasm Invasiveness*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Stellate Cells / cytology*
  • Pancreatic Stellate Cells / metabolism
  • RNA Interference
  • Reactive Oxygen Species / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Xanthones / pharmacology*
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • Transcription Factors
  • Xanthones
  • Zinc Finger Protein GLI1
  • mangostin