0 8 Daidzein Daidzein NNP 9 12 and and CC 13 22 genistein genistein NN 23 35 glucuronides glucuronide NNS 36 38 in in FW 39 44 vitro vitro FW 45 48 are be VBP 49 55 weakly weakly RB 56 66 estrogenic estrogenic JJ 67 70 and and CC 71 79 activate activate VBP 80 85 human human JJ 86 93 natural natural JJ 94 100 killer killer NN 101 106 cells cell NNS 107 109 at at IN 110 123 nutritionally nutritionally RB 124 132 relevant relevant JJ 133 147 concentrations concentration NNS 147 148 . . . 150 158 Daidzein Daidzein NNP 159 162 and and CC 163 172 genistein genistein NN 173 185 glucuronides glucuronide NNS 186 187 ( ( ( 187 189 DG DG NNP 190 193 and and CC 194 196 GG GG NNP 196 197 ) ) ) 197 198 , , , 199 204 major major JJ 205 215 isoflavone isoflavone NN 216 227 metabolites metabolite NNS 227 228 , , , 229 232 may may MD 233 235 be be VB 236 242 partly partly RB 243 254 responsible responsible JJ 255 258 for for IN 259 269 biological biological JJ 270 277 effects effect NNS 278 280 of of IN 281 292 isoflavones isoflavone NNS 292 293 , , , 294 298 such such JJ 299 301 as as IN 302 310 estrogen estrogen NN 311 319 receptor receptor NN 320 327 binding binding NN 328 331 and and CC 332 339 natural natural JJ 340 346 killer killer NN 347 351 cell cell NN 352 353 ( ( ( 353 355 NK NK NNP 355 356 ) ) ) 357 367 activation activation NN 368 370 or or CC 371 381 inhibition inhibition NN 381 382 . . . 383 385 DG DG NNP 386 389 and and CC 390 392 GG GG NNP 393 397 were be VBD 398 409 synthesized synthesize VBN 410 415 using use VBG 416 444 3-methylcholanthrene-induced 3-methylcholanthrene-induced JJ 445 448 rat rat NN 449 454 liver liver NN 455 465 microsomes microsome NNS 465 466 . . . 467 470 The the DT 471 473 Km Km NNP 474 477 and and CC 478 482 Vmax Vmax NNP 483 486 for for IN 487 495 daidzein daidzein NN 496 499 and and CC 500 509 genistein genistein NN 510 514 were be VBD 515 518 9.0 9.0 CD 519 522 and and CC 523 526 7.7 7.7 CD 527 537 micromol/L micromol/l NN 537 538 , , , 539 542 and and CC 543 546 0.7 0.7 CD 547 550 and and CC 551 554 1.6 1.6 CD 555 567 micromol/(mg micromol/(mg NN 568 576 protein. protein. NN 577 580 min min NN 580 581 ) ) ) 581 582 , , , 583 595 respectively respectively RB 595 596 . . . 597 600 The the DT 601 608 absence absence NN 609 611 of of IN 612 623 ultraviolet ultraviolet JJ 624 634 absorbance absorbance NN 635 641 maxima maxima NN 642 648 shifts shift NNS 649 651 in in IN 652 655 the the DT 656 664 presence presence NN 665 667 of of IN 668 674 sodium sodium NN 675 682 acetate acetate NN 683 692 confirmed confirm VBD 693 697 that that IN 698 701 the the DT 702 713 synthesized synthesize VBN 714 722 products product NNS 723 727 were be VBD 728 744 7-O-glucuronides 7-o-glucuronide NNS 744 745 . . . 746 748 DG DG NNP 749 752 and and CC 753 755 GG GG NNP 756 760 were be VBD 761 768 further further RB 769 777 purified purify VBN 778 780 by by IN 781 782 a a DT 783 791 Sephadex Sephadex NNP 792 797 LH-20 LH-20 NNP 798 804 column column NN 804 805 . . . 806 808 DG DG NNP 809 812 and and CC 813 815 GG GG NNP 816 824 competed compete VBD 825 829 with with IN 830 833 the the DT 834 841 binding binding NN 842 844 of of IN 845 856 17beta-(3H) 17beta-(3h) 17beta-(3H) 857 866 estradiol estradiol NN 867 869 to to TO 870 878 estrogen estrogen NN 879 888 receptors receptor NNS 889 891 of of IN 892 898 B6D2F1 b6d2f1 NN 899 904 mouse mouse NN 905 912 uterine uterine JJ 913 920 cytosol cytosol NN 920 921 . . . 922 925 The the DT 926 940 concentrations concentration NNS 941 949 required require VBN 950 953 for for IN 954 956 50 50 CD 956 957 % % NN 958 970 displacement displacement NN 971 973 of of IN 974 985 17beta-(3H) 17beta-(3h) 17beta-(3H) 986 995 estradiol estradiol NN 996 997 ( ( ( 997 1001 CB50 CB50 NNP 1001 1002 ) ) ) 1003 1007 were be VBD 1007 1008 : : : 1009 1025 17beta-estradiol 17beta-estradiol NN 1025 1026 , , , 1027 1031 1.34 1.34 CD 1032 1038 nmol/L nmol/l NN 1038 1039 ; ; : 1040 1058 diethylstilbestrol diethylstilbestrol NN 1058 1059 , , , 1060 1064 1.46 1.46 CD 1065 1071 nmol/L nmol/l NN 1071 1072 ; ; : 1073 1081 daidzein daidzein NN 1081 1082 , , , 1083 1086 1.6 1.6 CD 1087 1097 micromol/L micromol/l NN 1097 1098 ; ; : 1099 1101 DG DG NNP 1101 1102 , , , 1103 1107 14.7 14.7 CD 1108 1118 micromol/L micromol/l NN 1118 1119 ; ; : 1120 1129 genistein genistein NN 1129 1130 , , , 1131 1136 0.154 0.154 CD 1137 1147 micromol/L micromol/l NN 1147 1148 ; ; : 1149 1151 GG GG NNP 1151 1152 , , , 1153 1157 7.27 7.27 CD 1158 1168 micromol/L micromol/l NN 1168 1169 . . . 1170 1172 In in IN 1173 1178 human human JJ 1179 1189 peripheral peripheral JJ 1190 1195 blood blood NN 1196 1198 NK nk NN 1199 1204 cells cell NNS 1204 1205 , , , 1206 1215 genistein genistein NN 1216 1218 at at IN 1219 1223 <0.5 <0.5 CD 1224 1234 micromol/L micromol/l NN 1235 1238 and and CC 1239 1241 DG DG NNP 1242 1245 and and CC 1246 1248 GG GG NNP 1249 1251 at at IN 1252 1258 0.1-10 0.1-10 CD 1259 1269 micromol/L micromol/l NN 1270 1278 enhanced enhance VBD 1279 1281 NK nk NN 1282 1295 cell-mediated cell-mediated JJ 1296 1300 K562 k562 NN 1301 1307 cancer cancer NN 1308 1312 cell cell NN 1313 1320 killing killing NN 1321 1334 significantly significantly RB 1335 1336 ( ( ( 1336 1337 P p NN 1338 1339 < < SYM 1340 1344 0.05 0.05 CD 1344 1345 ) ) ) 1345 1346 . . . 1347 1349 At at IN 1350 1351 > > JJR 1352 1355 0.5 0.5 CD 1356 1366 micromol/L micromol/l NN 1366 1367 , , , 1368 1377 genistein genistein NN 1378 1387 inhibited inhibit VBD 1388 1390 NK NK NNP 1391 1403 cytotoxicity cytotoxicity NN 1404 1417 significantly significantly RB 1418 1419 ( ( ( 1419 1420 P p NN 1421 1422 < < SYM 1423 1427 0.05 0.05 CD 1427 1428 ) ) ) 1428 1429 . . . 1430 1433 The the DT 1434 1446 glucuronides glucuronide NNS 1447 1451 only only RB 1452 1461 inhibited inhibit VBD 1462 1464 NK NK NNP 1465 1477 cytotoxicity cytotoxicity NN 1478 1480 at at IN 1481 1483 50 50 CD 1484 1495 micromol/L. micromol/l. NN 1496 1507 Isoflavones isoflavone NNS 1507 1508 , , , 1509 1512 and and CC 1513 1523 especially especially RB 1524 1527 the the DT 1528 1538 isoflavone isoflavone NN 1539 1551 glucuronides glucuronide NNS 1551 1552 , , , 1553 1561 enhanced enhance VBD 1562 1572 activation activation NN 1573 1575 of of IN 1576 1578 NK NK NNP 1579 1584 cells cell NNS 1585 1587 by by IN 1588 1601 interleukin-2 interleukin-2 NN 1602 1603 ( ( ( 1603 1607 IL-2 il-2 NN 1607 1608 ) ) ) 1608 1609 , , , 1610 1620 additively additively RB 1620 1621 . . . 1622 1624 At at IN 1625 1638 physiological physiological JJ 1639 1653 concentrations concentration NNS 1653 1654 , , , 1655 1657 DG DG NNP 1658 1661 and and CC 1662 1664 GG GG NNP 1665 1669 were be VBD 1670 1676 weakly weakly RB 1677 1687 estrogenic estrogenic JJ 1687 1688 , , , 1689 1692 and and CC 1693 1697 they they PRP 1698 1707 activated activate VBD 1708 1713 human human JJ 1714 1716 NK nk NN 1717 1722 cells cell NNS 1723 1725 in in IN 1726 1739 nutritionally nutritionally RB 1740 1748 relevant relevant JJ 1749 1763 concentrations concentration NNS 1764 1766 in in FW 1767 1772 vitro vitro FW 1772 1773 , , , 1774 1782 probably probably RB 1783 1785 at at IN 1786 1787 a a DT 1788 1792 site site NN 1793 1802 different different JJ 1803 1807 from from IN 1808 1812 IL-2 il-2 NN 1813 1819 action action NN 1819 1820 . . .