Genistein Modulates Immune Responses and Increases Host Resistance to B16F10 Tumor in Adult Female B6C3F1 Mice

Abstract

The isoflavone genistein (4,7,4'-trihydroxyisoflavone) is a phytoestrogen found in high levels in soy products that has been associated with decreased incidences of breast and prostate cancers. The potential effects of genistein on the immune system were evaluated in adult female B6C3F1 mice. Groups of mice were exposed to vehicle or genistein by gavage for 28 d. The doses of genistein used were 2, 6 and 20 mg/kg body. Consistent with the chemopreventive effect of genistein, exposure to this compound significantly increased host resistance to B16F10 tumor as reflected by a decrease in the number of lung tumor nodules after tumor cell injection at the middle and high dose levels. Inhibition of B16F10 tumor formation was not due to a direct effect of serum genistein and/or its metabolites on the proliferation of B16F10 tumor cells. When innate and acquired immune responses were evaluated, a dose-related increase of cytotoxic T-cell activity was observed in genistein-treated mice with significant changes observed at the middle and high dose levels. Furthermore, in vitro interleukin (IL)-2-stimulated natural killer (NK) cell activity was significantly enhanced in the high genistein dose group, although the basal NK cell activity was not affected. Although no affect on the mixed lymphocyte responses and anti-CD3 antibody-mediated splenocyte proliferation was observed, exposure to genistein significantly increased basal splenocyte proliferation. Exposure to genistein did not alter the activity of the mononuclear phagocyte system and the cytotoxic/cytostatic function of thioglycollate-recruited peritoneal cells on B16F10 tumor cells. Finally, exposure to genistein did not produce biologically meaningful changes in spleen immunoglobulin (Ig)M and IgG antibody-forming cell responses. In conclusion, genistein enhanced host resistance as evaluated in the B16F10 tumor model, which may be related to the increases in the activities of cytotoxic T cells and NK cells.

Influence of Dietary Soy Phytoestrogens on Cytokine Production and Immunoglobulin in Ovariectomized Rats

“…Although genistein increased IgM at the dose of 6 mg/kg in adult female B6C3F1 mice, no effect was observed in the high dose group. Furthermore, exposure to genistein had no effect on IgG response [23]. Oral administration of daidzein to Swiss mice increased the thymic mass and number of lymphocytes in blood and resulted in elevated antigen-specific IgM [24].…”

“…The functions of T cells and NK cells were altered after oral exposure to genistein at physiologically relevant concentrations in experimental animals. Specifically, exposure to genistein in adult female mice for 28 days by gavage increased the activities of cytotoxic T cells and NK cells [23].…”

The role of environmental estrogens and autoimmunity

“…It is worthy to underline that soy is found in up to 60% of processed food, being a food additive and a meat substitute. Genistein and daidzein are the two most well characterized isoflavones [19,20].…”

Fermented Soybean Powder with Rice Mold in the Absence of Salt Stimulates the Cellular Immune System and Suppresses the Humoral Immune Response in Mice

“…Using a high performance liquid chromatography, we previously estimated that the levels of the glycoside types of genistein and daidzein in NSBP are 20.7 and 35.4 ppm, while the levels of the aglycone types are 118.0 and 188.0 ppm, respectively. Zhang et al reported that daidzein enhances the phagocytic activity in mice (27), while Guo et al reported that genistein increases the activity of cytotoxic T cells and NK cells in mice (28). It is demonstrated that the content of total daidzein and genistein of the fermented soybean without salt was increased more than that with 10% salt, presumably resulting from the low level of metabolical activation of Aspergillus oryzae under such a high salt content (29).…”