title: Histone deacetylase inhibitors induce human renal cell carcinoma cell apoptosis through p-JNK activation.
abstract: OBJECTIVE
  To study the effect of histone deacetylase inhibitors trichostatin A (TSA) and LBH589 on the growth of human renal cell carcinoma OS-RC-2 cells in vitro and explore the underlying molecular mechanism.
  
  
  METHODS
  OS-RC-2 cells were treated with LBH589 or TSA with or without SP600125 pretreatment, and the cell viability was measured by MTT assay. The changes of cell cycle distribution and apoptosis of OS-RC-2 cells were examined by flow cytometry, and the expressions of c-Jun, p-c-Jun, Bcl-2, and Bax were quantified by Western blotting.
  
  
  RESULTS
  TSA and LBH589 both inhibited the growth of OS-RC-2 cells in a dose- and time-dependent manner. TSA at 1 µnmol/L and LBH589 at 50 nmol/L caused obvious cell cycle arrest in G2/M phase and cell apoptosis, and significantly increased the protein levels of phosphorylated c-Jun. TSA treatment obviously increased Bax expression but decreased Bcl2 expression in the cells. The growth inhibitory effect of TSA was attenuated by the JNK inhibitor SP600125 in OS-RC-2 cells. TSA-induced phosphorylation of c-Jun and Bax upregulation was partially counteracted by SP600125.
  
  
  CONCLUSIONS
  TSA and LBH589 can cause cell cycle arrest and induce apoptosis in OS-RC-2 cells, in which process P-JNK pathway plays an important role.
authors.affiliation: Department of Internal Medicine, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. E-mail: gyeyxu@163.com.
authors.forename: Miqing
authors.initials: M
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Hong
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D000077767:Panobinostat; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; C012589:trichostatin A; D000077767:Panobinostat; D048031:JNK Mitogen-Activated Protein Kinases