Testosterone, lycopene isomers, and prostate cancer

Epidemiologic and laboratory studies have associated dietary intake of lycopene (the red pigment in tomatoes), serum testosterone concentrations, and energy balance with prostate cancer risk and progression. The objectives of our studies were first to determine the interactions between testosterone and diet restriction on lycopene tissue distribution and isomer patterns in rats and then to ultimately determine the influence of purified lycopene, whole tomato powder and diet restriction on chemically-induced prostate cancer in rats. In study #1, castrated (castrated at 5 wk of age) (n = 44) and intact (n = 44) male F344 rats were randomly assigned to one of four dietary lycopene groups (n = 11/diet): 0.00, 0.05, 0.50, and 5.00 g/kg lycopene and fed for 8 weeks. Serum and tissue lycopene was analyzed by HPLC. Surprisingly, castrated rats accumulated 2.3-fold more liver lycopene (P < 0.01) and significantly more hepatic cis-lycopene isomers (P < 0.05) than intact rats at all dietary lycopene concentrations despite lower intake. Serum lycopene was not significantly altered by castration.; In study #2, intact (n = 10), castrates (n = 10), castrated rats given testosterone implants (n = 10), and intact rats diet restricted to castrate intake (n = 10) were fed 0.25 g/kg lycopene for three weeks. As previously observed, castrates accumulated 2-fold more hepatic lycopene than intact ad libitum fed rats (P < 0.05). Testosterone replacement to castrated rats significantly (P < 0.05) increased serum testosterone and resulted in hepatic lycopene accumulation similar to intact ad libitum fed rats. Diet restriction significantly (P < 0.05) decreased serum testosterone (P < 0.05 vs intact ad libitum) and consequently increased (P < 0.05) hepatic lycopene.; The objective of the final study was to determine the influence of purified lycopene, tomato powder, and 20% diet restriction on N-methyl-N-nitrosourea (NMU)-testosterone-induced prostate cancer in rats. Survival was analyzed to include only rats that died with adenocarcinomas of the accessory sex glands. Only tomato powder-fed (RR = 0.570; P = 0.009) rats experienced significantly increased survival as compared to placebo beadlet-fed control rats. No significant influences of lycopene beadlet feeding or diet restriction as well as no interactions were noted for accessory sex gland-specific survival. We conclude that tomato powder may contain compounds, in addition to lycopene, which favorably modulate prostate carcinogenesis.