title: Thiazolidenediones induce tumour-cell apoptosis through the Akt-GSK3β pathway.
abstract: OBJECTIVE
  Prostate cancer is a major health threat for men. Thiazolidenediones (TZDs) are synthetic ligands of the peroxisome proliferator-activated receptor γ (PPARγ), and previous studies have shown that TZDs induce apoptosis of prostate cancer cells independently of PPARγ activation. However, the exact mechanism of these effects remains unknown. Our objective was to investigate the effects of TZDs on apoptosis and on the serine/threonine kinase pathway, Akt, and glycogen synthase kinase 3β (GSK3β).
  
  
  METHODS
  LNCaP cells, a type of prostate cancer cells (derived from left supraclavicular lymph node of human prostrate carcinoma), were cultured in DMEM medium, and cell viability was evaluated with a colorimetric assay using MTT level. The total and phosphorylated protein level of Akt and GSK3β were detected by Western blotting.
  
  
  CONCLUSIONS
  The apoptosis-inducing effect of TZDs on prostate cancer cells involves the inhibition of Akt phosphorylation. Furthermore, TZDs induce inactivation of GSK3β, a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. In addition, the GSK3β inhibitor lithium chloride sensitizes prostate cancer cells to TZDs cytotoxicity.
  
  
  CONCLUSIONS
  Our data suggest that modulation of Akt-GSK3β pathway is involved in the cell death pathway engaged by TZDs in prostate cancer cells. This reveals another possible mechanism of TZDs on apoptosis in prostate cancer. Inhibition of the Akt-GSK3β cascade may be a useful approach in prostate cancer.
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao University, Qingdao, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Qi
authors.forename: L
authors.initials: L
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003124:Colorimetry; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D045162:Thiazolidinediones; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride