Doxorubicin (DOX=adriamycine), an effective chemotherapeutic agents for can
cers, has severe cardiotoxicity. In the paresent study, we examined the pro
tective effect of thermal preconditioning (TP) against apoptosis of rat car
diac muscle cells induced by DOX. Treatment with DOX (10 mu M) for 24 hrs r
esulted in apoptosis of cardiac muscle cells, which was evaluated by examin
ing "DNA ladder" formation and TUNEL staining. The number of TUNEL-positive
cells was significantly decreased in cells subjected to TP by incubation a
t 42 degrees C for 30 min, 24 hrs prior to DOX-treatment. Antisense oligonu
cleotides of the heat shock protein (HSP) 70 blunted this effect. These res
ults indicate that DOX-induced apoptosis in cardiac muscle cells is prevent
ed by TP, at least in part, via a HSP70-mediated mechanism.