Rosiglitazone regulates anti-inflammation and growth inhibition via PTEN.
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.
Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Chiou-Feng
CF
Lin
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Kung-Chia
KC
Young
School of Public Health, Taipei Medical University, Taipei 11031, Taiwan.
Chyi-Huey
CH
Bai
Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Bu-Chin
BC
Yu
Institute 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.
Ching-Ting
CT
Ma
Department 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.
Yu-Chieh
YC
Chien
Department of Nursing, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te Hsiang, Tainan 71703, Taiwan.
Chiu-Ling
CL
Chiang
Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.
Chao-Sheng
CS
Liao
Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.
Hsin-Wen
HW
Lai
Department of Nursing, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te Hsiang, Tainan 71703, Taiwan.
Chiung-Wen
CW
Tsao
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009569:Nitric Oxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse