Inhibition of orthotopic growth and metastasis of androgen-sensitive human prostate tumors in mice by bioactive soybean components

BACKGROUND. Systematic analysis of the influence of diet on the initiation and progression of prostate cancer is often difficult in human populations, for which dietary variables overlap a diversity of genetic backgrounds and social behaviors. Animal models that emulate human prostate cancer allow experimental analysis of the mechanisms of action of nutritional agents that show anti-prostate cancer activity. METHODS. We have used an orthotopic implant model to characterize the in vivo response of androgen-sensitive LNCaP prostate tumors to three well-characterized soy dietary supplements: isoflavone depleted soy protein, soy phytochemical concentrate (SPC), and genistin. RESULTS. In male SCID mice orthotopically implanted with the androgen-sensitive human prostate cell line LNCaP, dietary supplements of soy protein, genistin, and SPC reduced primary tumor weight by 42% (P = 0.07), 57% (P < 0.05) and 70% (P < 0.005), respectively. All three soy supplements significantly increased tumor apoptosis and decrease microvessel density, with no significant change in tumor proliferation. Each supplement produced a distinct serum androgen response, with genistin producing the greatest decrease in total serum testosterone and dihydrotestosterone (DHT) (P < 0.05) and the greatest increase in testosterone to DHT ratio (P <0.05) and soy protein the greatest decrease in bioactive androgen (P < 0.05). Only SPC significantly inhibited metastases to lymph nodes and lungs, and only SPC produced a significant increase in tumor p53 expression. CONCLUSION. Taken together, these data suggest that the anti-prostate cancer activity of dietary soy protein, soy phytochemicals, and genistin use different molecular pathways. In addition, we have demonstrated that this animal model can be used in the design of dietary strategies for prostate cancer prevention and therapy. (C) 2002 Wiley-Liss, Inc.