Genistein Inhibits Growth of Estrogen-Independent Human Breast Cancer Cells in Culture but Not in Athymic Mice

Abstract

The studies presented were conducted to assess the effect of the soy isoflavone genistein on proliferation of estrogen-independent human breast cancer cells (MDA-MB-231) in vitro and in vivo. Genistein (20 mcmol/L) inhibited cell proliferation in vitro by approximately 50%. Cell cycle progression was blocked in G(2)/M with 40 and 80 mcmol/L genistein. To evaluate the effect of dietary genistein on tumor growth in vivo, genistein was fed to female athymic mice inoculated with MDA-MB-231 cells. After solid tumor masses had formed, mice were fed genistein at a dose (750 mcg/g AIN-93G diet), shown to produce a total plasma genistein concentration of approximately 1 mcmol/L. This dose of genistein did not significantly (P > 0.05) alter tumor growth. Studies were then conducted to assess the effect of dietary genistein on initial tumor development and growth. Genistein (750 mcg/g AIN-93G diet), fed 3 d before cells were inoculated into mice, did not significantly (P > 0.05) inhibit tumor formation or growth. The plasma concentration of genistein in mice fed this dose of dietary genistein (750 mcg/g AIN-93G diet) does not appear sufficient to inhibit tumor formation or growth. Dietary genistein at 750 mcg/g AIN-93G diet does not inhibit tumor formation or growth. Additional studies were conducted to determine the effect of dietary dosages ranging from 0 to 6000 mcg/g AIN-93G diet on plasma genistein concentration. Plasma genistein concentration increased in a dose-dependent manner up to 7 mcmol/L at 6000 mcg/g AIN-93G diet. These data suggest that although genistein inhibits cancer cell growth in vitro, it is unlikely that the plasma concentration required to inhibit cancer cell growth in vivo can be achieved from a dietary dosage of genistein.

The phytoestrogen genistein induces thymic and immune changes: A human health concern?

“…Body weight was not different in control and 1,000 ppm genistein groups and was slightly (Ͻ5%) lower in the 1,500 ppm group compared with controls. These results are consistent with previous reports that dietary genistein at 1,000 ppm did not affect body weight (22) and that genistein at 1,000 or 1,500 ppm did not affect food consumption (22,23). Serum genistein levels in mice fed 1,000 and 1,500 ppm genistein were 0.97 Ϯ 0.04 and 1.12 Ϯ 0.18 M, respectively, whereas genistein was not measurable in 17͞18 control samples (Fig.…”

Phytoestrogens and breast cancer –promoters or protectors?

“…In contrast, Shao et al (1998) reported that genistein inhibited growth of these ER-positive and ER-negative xenografts and stimulated apoptosis. Similar anti-tumor effects have also been seen in chemically induced mammary carcinogenesis (Barnes et al 1990, Lamartiniere et al 1998, Constantinou et al 2001) and nude mice (Constantinou et al 1998), although Santell et al (2000) found no growth-inhibitory effects of genistein in vivo, even when relatively high circulating plasma concentrations were achieved. In MMTV/neu transgenic mice, there were no significant differences in the tumor latency between low-and high-dose isoflavone diets nor in the percentage of disease-free mice at 60 weeks.…”

Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model

“…In rats, genistein is known to reach bone in approximately 17 times lower quantities when compared to plasma levels, 2 h after administration of 4 mg/kg genistein (Coldham and Sauer 2000) (in the current study, we used 160 mg/kg/day oral supplementation). Although plasma genistein concentrations in our study were comparable with or even higher than the concentrations reported in other studies on the effects of genistein in mice (Santell et al 2000;Mentor-Marcel et al 2001), genistein concentrations in the bone in our study were below detection level. These results suggest that the treatment duration and/or dosage of genistein may have been insufficient to treat the bone.…”