Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biomed Res Int. 2014;2014:787924. doi: 10.1155/2014/787924. Epub 2014 Mar 13.

Rosiglitazone regulates anti-inflammation and growth inhibition via PTEN.

Author information

  • 1Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
  • 2Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
  • 3School of Public Health, Taipei Medical University, Taipei 11031, Taiwan.
  • 4Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
  • 5Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan 70101, Taiwan ; Department of Nursing, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te Hsiang, Tainan 71703, Taiwan.
  • 6Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan ; Department of Nursing, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te Hsiang, Tainan 71703, Taiwan.
  • 7Department of Nursing, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te Hsiang, Tainan 71703, Taiwan.
  • 8Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) agonist has anti-inflammatory and anticancer properties. However, the mechanisms by which PPARγ agonist rosiglitazone interferes with inflammation and cancer via phosphatase and tensin homolog-(PTEN)-dependent pathway remain unclear. We found that lower doses (<25  μ M) of rosiglitazone significantly inhibited lipopolysaccharide-(LPS)-induced nitric oxide (NO) release (via inducible nitric oxide synthase, iNOS), prostaglandin E2 (PGE2) production (via cyclooxygenase-2, COX-2), and activation of Akt in RAW 264.7 murine macrophages. However, rosiglitazone did not inhibit the production of reactive oxygen species (ROS). In PTEN knockdown (shPTEN) cells exposed to LPS, rosiglitazone did not inhibit NO release, PGE2 production, and activation of Akt. These cells had elevated basal levels of iNOS, COX-2, and ROS. However, higher doses (25-100  μ M) of rosiglitazone, without LPS stimulation, did not block NO release and PGE2 productions, but they inhibited p38 MAPK phosphorylation and blocked ROS generation in shPTEN cells. In addition, rosiglitazone caused G1 arrest and reduced the number of cells in S + G2/M phase, leading to growth inhibition. These results indicate that the anti-inflammatory property of rosiglitazone is related to regulation of PTEN independent of inhibition on ROS production. However, rosiglitazone affected the dependence of PTEN-deficient cell growth on ROS.

PMID:
24757676
[PubMed - indexed for MEDLINE]
PMCID:
PMC3971553
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Hindawi Publishing Corporation Icon for PubMed Central
    Loading ...
    Write to the Help Desk