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a Department of Food Science and Human Nutrition and b Department of Microbiology, Iowa State University, Ames, IA 50011
Daidzein and genistein glucuronides (DG and GG), major isoflavone metabolites, may be partly responsible for biological effects of isoflavones, such as estrogen receptor binding and natural killer cell (NK) activation or inhibition. DG and GG were synthesized using 3-methylcholanthrene-induced rat liver microsomes. The Km and Vmax for daidzein and genistein were 9.0 and 7.7 µmol/L, and 0.7 and 1.6 µmol/(mg protein · min), respectively. The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O-glucuronides. DG and GG were further purified by a Sephadex LH-20 column. DG and GG competed with the binding of 17ß-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol. The concentrations required for 50% displacement of 17ß-(3H) estradiol (CB50) were: 17ß-estradiol, 1.34 nmol/L; diethylstilbestrol, 1.46 nmol/L; daidzein, 1.6 µmol/L; DG, 14.7 µmol/L; genistein, 0.154 µmol/L; GG, 7.27 µmol/L. In human peripheral blood NK cells, genistein at <0.5 µmol/L and DG and GG at 0.1–10 µmol/L enhanced NK cell-mediated K562 cancer cell killing significantly (P < 0.05). At > 0.5 µmol/L, genistein inhibited NK cytotoxicity significantly (P < 0.05). The glucuronides only inhibited NK cytotoxicity at 50 µmol/L. Isoflavones, and especially the isoflavone glucuronides, enhanced activation of NK cells by interleukin-2 (IL-2), additively. At physiological concentrations, DG and GG were weakly estrogenic, and they activated human NK cells in nutritionally relevant concentrations in vitro, probably at a site different from IL-2 action.
KEY WORDS: • isoflavones • glucuronides • estrogen • human natural killer cell
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