Lycopene is a promising chemopreventive agent for human prostate cancer. To test the hypothesis that the effect of lycopene on prostate cancer is stage specific in the process of carcinogenesis, inhibitory effects of natural lycopene on the proliferation of 3 different human prostate carcinoma cell lines were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Lycopene more potently inhibited the growth of the androgen-independent DU145 and PC-3 cells than androgen-dependent LNCaP cells. The 50% inhibitory concentration of lycopene for these cell lines was 26.6 micromol/L for DU145, 40.3 micromol/L for PC-3, and 168.5 micromol/L for LNCaP. We also studied the inhibitory effect of lycopene on the growth rate of DU145 tumor xenografts in BALB/c male nude mice. The tumor growth rate was inhibited by 55.6 and 75.8% in mice treated with 100 and 300 mg/kg lycopene, respectively, compared with controls. In addition, no tumors formed in 1 mo in mice treated with DU145 cells that had been pretreated with 20 micromol/L lycopene; however, they did form when DU145 cells were not pretreated. Flow cytometry revealed that lycopene caused DU145 cells to accumulate in the G(0)/G(1) phase and to undergo apoptosis in a dose-dependent manner. The rate of apoptosis was up to 42.4% lower in DU145 cells treated with 32 micromol/L lycopene compared with the untreated control cells. These results suggest that lycopene may specifically inhibit the growth of androgen-independent prostate cancers.