Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.
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.
Matsumoto
H
H
Department of Experimental Radiology & Health Physics, Fukui Medical University, Matsuoka, Japan.
Hayashi
S
S
Shioura
H
H
Ohtsubo
T
T
Kitai
R
R
Ohnishi
K
K
Hayashi
N
N
Ohnishi
T
T
Kano
E
E
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
D000970:Antineoplastic Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D014157:Transcription Factors; D002945:Cisplatin