Effect of Genistein and Genistein Analogs on Growth of Human Prostate Tissue In Vitro

Abstract

that prostate disease is significantly less prevalent in Asia, where the intake of soy products is very high, than in the United States, where intake is low (Gu et al., 1994). We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human-patient benign prostatic hyperplasia (BPH) and prostate cancer tissue in three-dimensional sponge-gel supported histoculture (SSH) (Hoffman, 1998). More recently, we improved the sensitivity of the histoculture method by the use of total immersion in the histoculture medium; we have called this technique total immersion histoculture (TIH) (Olbina et al, 1998).Surgical specimens of human BPH and cancer were histocultured with the SSH and TIH techniques in parallel for 5 days to study the effect of genistein on growth, as measured by inhibition of 3-H-thymidine incorporation per microgram of protein on day 5. RESULTS AND DISCUSSIONWe compared inhibition of growth after treatment of BPH and cancer tissue with genistein in SSH or TIH. Inhibition of growth was expressed as percentage of control growth of the tissue treated with dihydrotestosterone (DHT) alone. Incorporation of 3H-thymidine dramatically increased in control histocultures, by twofold to fivefold, in TIH compared with the same tissue in SSH (Fig. 1).We observed significantly increased growth inhibition of BPH and cancer tissue treated with 18.4 /xmol/L of genistein with TIH, compared with SSH. The average inhibition in TIH was 73% (range 67-79%), compared with a mean decrease of 31% (range 6-68%) in SSH (Fig. 2). This inhibition was statistically significant (P < .05).To examine the sensitivity of TIH, we treated BPH and cancer tissue in TIH with decreasing concentrations of genistein. We observed 40% growth inhibition of tissue treated with 4.6 /¿mol/L and 26% inhibition with 2.3 /¿mol/L, with a mean coefficient of variation (CV) of 13%. Both of these values represent significant differences (P < .05). In contrast, inhibition was not significant with concentrations lower than 9.2 ¿imol/L genistein in SSH (CV range, 8-29%) (Fig. 3).Inhibitory effects on 3H-thymidine incorporation of 20 ¿tmol/L of hydroxyflutamide, a known antiandrogen, were compared using the same tissue in SSH and TIH. In all experiments, the incorporation of 3H-thymidine was three to four times higher for TIH in control histocultures. The inhibition caused by 2 x 10-5 mol/L hydroxyflutamide was 40-60% in TIH. In SSH, inhibition by 2 X 10-5 mol/L hydroxyflutamide was 17-18%, and in some experiments it was not detectable to all.