ASPIRIN ENHANCES THERMOTOLERANCE IN HUMAN ERYTHROLEUKEMIC CELLS - AN EFFECT ASSOCIATED WITH THE MODULATION OF THE HEAT-SHOCK RESPONSE

Heat shock protein (HSP) synthesis is induced by hyperthermia and othe r types of stress in mammalian cells in vitro and in vivo. In the pres ent report we describe that in human erythroleukemic cells, aspirin (4 00 mu M), 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 D NA-binding state for a period twice as long as control, an effect whic h results in enhanced and prolonged HSP70 mRNA transcription. A differ ent cyclooxygenase inhibitor, indomethacin (10(-7) M), also provokes s imilar effects. The modulation of the heat shock response by aspirin a nd indomethacin is associated with the ability of these drugs to poten tiate the effect of hyperthermia and prolong thermotolerance for a per iod of 48 h. These results indicate that the use of aspirin and indome thacin should be carefully monitored in cancer patients undergoing hyp erthermic treatment. On the other hand, the ability of aspirin to enha nce HSP70 synthesis suggests that nonsteroidal anti-inflammatory drugs could potentiate the cytoprotective role of HSPs in pathological stat es, including fever, inflammation, and ischemia.