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

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.

• Authors: Jianjun Lei, Xiongwei Huo, Wanxing Duan, Qinhong Xu, Rong Li, Jiguang Ma, Xuqi Li, Liang Han, Wei Li, Hao Sun, Erxi Wu, Qingyong Ma
• Journal: Cancer letters (Cancer Lett) Vol. 347 Issue 1 Pg. 129-38 (May 28 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 24513179 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

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