Rosiglitazone Regulates Anti-Inflammation and Growth Inhibition via PTEN
| Autor: | Bu Chin Yu, Chao Sheng Liao, Hsin Wen Lai, Ching Ting Ma, Kung Chia Young, Chiung Wen Tsao, Yu Chieh Chien, Chiou Feng Lin, Chiu Ling Chiang, Chyi Huey Bai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Article Subject lcsh:Medicine Nitric Oxide General Biochemistry Genetics and Molecular Biology PPAR agonist Nitric oxide Cell Line Rosiglitazone chemistry.chemical_compound Mice Internal medicine medicine Tensin PTEN Animals Hypoglycemic Agents Protein kinase B General Immunology and Microbiology biology Macrophages Anti-Inflammatory Agents Non-Steroidal lcsh:R PTEN Phosphohydrolase General Medicine G1 Phase Cell Cycle Checkpoints Nitric oxide synthase PPAR gamma Endocrinology chemistry Cyclooxygenase 2 biology.protein Thiazolidinediones Growth inhibition Reactive Oxygen Species Proto-Oncogene Proteins c-akt medicine.drug Research Article |
| Zdroj: | BioMed Research International, Vol 2014 (2014) BioMed Research International |
| ISSN: | 2314-6133 |
| DOI: | 10.1155/2014/787924 |
| Popis: | Peroxisome proliferator-activated receptor gamma (PPARγ) agonist has anti-inflammatory and anticancer properties. However, the mechanisms by which PPARγagonist rosiglitazone interferes with inflammation and cancer via phosphatase and tensin homolog-(PTEN)-dependent pathway remain unclear. We found that lower doses (μM) 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, PGE2production, and activation of Akt. These cells had elevated basal levels of iNOS, COX-2, and ROS. However, higher doses (25–100 μM) of rosiglitazone, without LPS stimulation, did not block NO release and PGE2productions, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|