Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells.
BACKGROUND
It has been demonstrated that prostate cancer cells are relatively sensitive to heat stress. We have reported that heat treatment at 43 degrees C increases the expression of heat shock protein 70 (hsp70) in prostate cancer cells, leading to apoptosis. Hsp70 is a protein that protects cells against heat damage. Cells with lower levels of hsp70 have been shown to have a higher sensitivity to heat stress. Therefore, downregulation of hsp70 is expected to enhance heat-induced inhibitory effects on cell growth. Quercetin has been reported to be an agent that inhibits hsp70 expression. The present study was undertaken to investigate the effects of quercetin and/or heat on the growth of prostate cancer cells in vitro.


METHODS
Three human prostate cancer cell lines were used: Lncap; PC-3; and JCA-1. The cells were treated with quercetin and/or heat. Alterations in the cell cycle and hsp70 expression were examined by means of flow cytometry (FCM). The apoptotic cells were detected by FCM using fluorescein isothiocyanate (FITC) labeled annexin V.


RESULTS
Treatment with quercetin alone resulted in an apparent decrease of hsp70-positive cells and an increase of subG1 cells in JCA-1 and LNcap cells. Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells. Quercetin was found to enhance heat-induced inhibitory effects on cell growth and heat-induced apoptosis in both JCA-1 and LNcap cells.


CONCLUSIONS
These results suggest that quercetin may enhance heat-induced cytotoxicity in prostate cancer cell lines through the inhibition of hsp70 production.
Nakanoma
T
T
Department of Urology, Saitama Medical School, Saitama, Japan. nakanoma@saitama-med.ac.jp
Ueno
M
M
Iida
M
M
Hirata
R
R
Deguchi
N
N
D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D011794:Quercetin