Hyperthermia is known to serve as a powerful tool in the treatment of
prostate cancer which is commonly diagnosed in men.
Quercetin and
KNK437, Hsp70 inhibitors, play an important role in blocking thermotolerance in some
cancer cells. In the present study we investigated the effects of
KNK437 and
quercetin on the acquisition of thermotolerance and heat-induced apoptosis. Also, it was examined whether the possible mechanism triggering apoptotic pathway included
caspase-3 activation in
prostate cancer cells. For this purpose, PC-3 and LNCaP cells were treated with
hyperthermia following pretreatment with or without
KNK437 or
quercetin. Thermotolerance was investigated by colony formation assay in these cells, while Hsp70
mRNA levels were measured by real time RT-PCR. Sandwich ELISA was used for detection of Hsp70
protein levels. Apoptosis was detected by flow cytometric
annexin V binding assay and by western blot analysis of
procaspase-3 and cleaved
poly (ADP-ribose) polymerase levels. In our study,
KNK437 and
quercetin inhibited thermotolerance in a dose-dependent manner in PC-3 cells.
KNK437 and
quercetin decreased heat-induced accumulation of Hsp70
mRNA and
protein in PC-3 and LNCaP cells.
KNK437 and
quercetin pretreatment enhanced the apoptotic effect of
hyperthermia in both cells. We found that
KNK437 was more effective than
quercetin in inducing apoptotic cell death, activation of
caspase-3, and cleavage of PARP in
prostate cancer cells. We suggest that
KNK437 is a useful agent for enhancing the efficiency of hyperthermic
therapy which has less toxic side-effects in
prostate cancer.