Flavonoids suppress androgen-independent human prostate tumor proliferation.
The present studies compared the effects of selected bioflavonoids on the proliferation of androgen-independent human prostatic tumor cells (PC-3). Complete growth retardation was observed in PC-3 cells treated with 100 microM quercetin, kaempferol, and luteolin, while isomolar genistein, apigenin, and myricetin suppressed PC-3 proliferation by 73%, 70%, and 59%, respectively (p < 0.05). Naringenin and rutin were not as effective and inhibited growth by < 25%. Exposure to increasing concentrations of quercetin and kaempferol led to a dose-dependent decrease in proliferation. Refeeding kaempferol-treated cells (50 microM) complete medium without the flavonoid resulted in a return toward control growth rates. Similar growth recovery was not observed in quercetin-treated cells. The antiproliferative response of PC-3 cells to quercetin and kaempferol was additive when supplemented to the medium at 25 microM. A block in G2-to-M phase progression was observed after the addition of 25 microM kaempferol. When quercetin reached 100 microM, an increase in the proportion of cells in the S phase became apparent within 24 hours. Apoptosis was not evident, even when concentrations of quercetin or kaempferol were raised to 100 microM. The present studies suggest that alterations in cell cycle progression contribute significantly to the antiproliferative effects of quercetin and kaempferol in PC-3 cells.
Knowles
L M
LM
Graduate Program in Nutrition, Nutrition Department, Pennsylvania State University, University Park, PA 16802, USA.
Zigrossi
D A
DA
Tauber
R A
RA
Hightower
C
C
Milner
J A
JA
D000728:Androgens; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000728:Androgens; D005419:Flavonoids