RT Journal Article
SR Electronic
T1 Aspirin Enhances Thermotolerance in Human Erythroleukemic Cells: An Effect Associated with the Modulation of the Heat Shock Response
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4452
OP 4457
VO 55
IS 19
A1 Amici, Carla
A1 Rossi, Antonio
A1 Santoro, M. Gabriella
YR 1995
UL http://cancerres.aacrjournals.org/content/55/19/4452.abstract
AB Heat shock protein (HSP) synthesis is induced by hyperthermia and other types of stress in mammalian cells in vitro and in vivo. In the present report we describe that in human erythroleukemic cells, aspirin (400 µm), when administered during or immediately after a hyperthermic treatment, causes an increase in the amount of HSP70 synthesized and prolongs HSP70 synthesis for a period of several hours. This effect is not due to increased HSP70 mRNA stability. In the presence of aspirin, the heat shock transcription factor is maintained in the activated DNA-binding state for a period twice as long as control, an effect which results in enhanced and prolonged HSP70 mRNA transcription. A different cyclooxygenase inhibitor, indomethacin (10-7 m), also provokes similar effects. The modulation of the heat shock response by aspirin and indomethacin is associated with the ability of these drugs to potentiate the effect of hyperthermia and prolong thermotolerance for a period of 48 h. These results indicate that the use of aspirin and indomethacin should be carefully monitored in cancer patients undergoing hyperthermic treatment. On the other hand, the ability of aspirin to enhance HSP70 synthesis suggests that nonsteroidal anti-inflammatory drugs could potentiate the cytoprotective role of HSPs in pathological states, including fever, inflammation, and ischemia. ©1995 American Association for Cancer Research.