title: Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.
abstract: OBJECTIVE
  The kinetics of the accumulation of inducible 72-kD heat shock protein (hsp72) and the activation of heat shock transcriptional factor (HSF) after hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172 having the wild-type p53 gene and T98G having the mutated p53 gene were evaluated.
  
  
  METHODS
  Western blot analysis of hsp72, gel-mobility shift assay of HSF, cell survival, and development of thermotolerance were examined.
  
  
  RESULTS
  The prominent suppression of heat-induced hsp72 accumulation by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53-dependent inhibition of heat-induced HSF activation by CDDP. The interactive hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but not in T98G cells. In addition, the heat-induced thermotolerance was suppressed by the presence of CDDP in the pretreatment.
  
  
  CONCLUSIONS
  Suppression of heat-induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.
authors.affiliation: Department of Experimental Radiology & Health Physics, Fukui Medical University, Matsuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Shioura
authors.forename: T
authors.initials: T
authors.lastname: Ohtsubo
authors.forename: R
authors.initials: R
authors.lastname: Kitai
authors.forename: K
authors.initials: K
authors.lastname: Ohnishi
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: E
authors.initials: E
authors.lastname: Kano
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D014157:Transcription Factors; D002945:Cisplatin