0 11 Pyrrolidine Pyrrolidine NNP 12 27 dithiocarbamate dithiocarbamate NN 27 28 , , , 29 30 a a DT 31 37 potent potent JJ 38 47 inhibitor inhibitor NN 48 50 of of IN 51 58 nuclear nuclear JJ 59 65 factor factor NN 66 71 kappa kappa NN 72 73 B B NNP 74 75 ( ( ( 75 83 NF-kappa NF-kappa NNP 84 85 B B NNP 85 86 ) ) ) 87 97 activation activation NN 97 98 , , , 99 107 prevents prevent VBZ 108 117 apoptosis apoptosis NN 118 120 in in IN 121 126 human human JJ 127 140 promyelocytic promyelocytic JJ 141 149 leukemia leukemia NN 150 155 HL-60 hl-60 NN 156 161 cells cell NNS 162 165 and and CC 166 176 thymocytes thymocyte NNS 176 177 . . . 179 181 We we PRP 182 190 examined examine VBD 191 194 the the DT 195 201 effect effect NN 202 204 of of IN 205 216 pyrrolidine pyrrolidine NN 217 232 dithiocarbamate dithiocarbamate NN 233 234 ( ( ( 234 238 PDTC PDTC NNP 238 239 ) ) ) 239 240 , , , 241 246 which which WDT 247 255 potently potently RB 256 262 blocks block VBZ 263 266 the the DT 267 277 activation activation NN 278 280 of of IN 281 288 nuclear nuclear JJ 289 295 factor factor NN 296 301 kappa kappa NN 302 303 B B NNP 304 305 ( ( ( 305 313 NF-kappa NF-kappa NNP 314 315 B B NNP 315 316 ) ) ) 316 317 , , , 318 320 on on IN 321 324 the the DT 325 334 induction induction NN 335 337 of of IN 338 347 apoptosis apoptosis NN 348 350 by by IN 351 352 a a DT 353 360 variety variety NN 361 363 of of IN 364 370 agents agent NNS 370 371 . . . 372 381 Treatment Treatment NNP 382 384 of of IN 385 386 a a DT 387 392 human human JJ 393 406 promyelocytic promyelocytic JJ 407 415 leukemia leukemia NN 416 420 cell cell NN 421 425 line line NN 425 426 , , , 427 432 HL-60 HL-60 NNP 432 433 , , , 434 438 with with IN 439 441 10 10 CD 442 455 micrograms/mL micrograms/ml NN 456 465 etoposide etoposide NN 466 468 or or CC 469 470 2 2 CD 471 477 microM microm NN 478 511 1-beta-D-arabinofuranosylcytosine 1-beta-d-arabinofuranosylcytosine NN 512 519 induced induce VBD 520 528 NF-kappa NF-kappa NNP 529 530 B B NNP 531 541 activation activation NN 542 548 within within IN 549 550 1 1 CD 551 553 hr hr NN 554 557 and and CC 558 570 subsequently subsequently RB 571 577 caused cause VBD 578 587 apoptosis apoptosis NN 588 594 within within IN 595 598 3-4 3-4 CD 599 601 hr hr NN 601 602 . . . 603 606 The the DT 607 619 simultaneous simultaneous JJ 620 628 addition addition NN 629 631 of of IN 632 638 50-500 50-500 CD 639 645 microM microM NNP 646 650 PDTC PDTC NNP 651 655 with with IN 656 661 these these DT 662 668 agents agent NNS 669 676 blocked block VBD 677 685 NF-kappa NF-kappa NNP 686 687 B B NNP 688 698 activation activation NN 699 702 and and CC 703 713 completely completely RB 714 723 abrogated abrogate VBD 724 728 both both CC 729 744 morphologically morphologically RB 745 754 apoptotic apoptotic JJ 755 762 changes change NNS 763 766 and and CC 767 783 internucleosomal internucleosomal JJ 784 787 DNA dna NN 788 801 fragmentation fragmentation NN 802 805 for for IN 806 808 up up RB 809 811 to to TO 812 813 6 6 CD 814 816 hr hr NN 816 817 . . . 818 825 However however RB 825 826 , , , 827 831 PDTC PDTC NNP 832 838 failed fail VBD 839 841 to to TO 842 849 inhibit inhibit VB 850 853 the the DT 854 866 endonuclease endonuclease NN 867 875 activity activity NN 876 885 contained contain VBN 886 888 in in IN 889 892 the the DT 893 898 whole whole JJ 899 903 cell cell NN 904 911 lysates lysate NNS 911 912 . . . 913 916 The the DT 917 927 inhibitory inhibitory JJ 928 934 effect effect NN 935 937 of of IN 938 942 PDTC PDTC NNP 943 946 was be VBD 947 951 also also RB 952 960 observed observe VBN 961 963 in in IN 964 974 etoposide- etoposide- NN 975 978 and and CC 979 1000 dexamethasone-induced dexamethasone-induced JJ 1001 1010 apoptosis apoptosis NN 1011 1013 in in IN 1014 1019 human human JJ 1020 1030 thymocytes thymocyte NNS 1031 1033 at at IN 1034 1035 a a DT 1036 1049 concentration concentration NN 1050 1052 of of IN 1053 1057 1-10 1-10 CD 1058 1064 microM microm NN 1064 1065 . . . 1066 1071 Since since IN 1072 1076 PDTC PDTC NNP 1077 1080 has have VBZ 1081 1085 both both CC 1086 1097 antioxidant antioxidant JJ 1098 1101 and and CC 1102 1111 metal-ion metal-ion JJ 1112 1121 chelating chelate VBG 1122 1132 activities activity NNS 1132 1133 , , , 1134 1136 we we PRP 1137 1143 tested test VBD 1144 1147 the the DT 1148 1155 effects effect NNS 1156 1158 of of IN 1159 1178 N-acetyl-L-cysteine N-acetyl-L-cysteine NNP 1179 1180 ( ( ( 1180 1183 NAC NAC NNP 1183 1184 ) ) ) 1185 1186 ( ( ( 1186 1197 antioxidant antioxidant JJ 1197 1198 ) ) ) 1199 1201 or or CC 1202 1218 o-phenanthroline o-phenanthroline NN 1219 1220 ( ( ( 1220 1222 OP OP NNP 1222 1223 ) ) ) 1224 1225 ( ( ( 1225 1234 metal-ion metal-ion NN 1235 1243 chelator chelator NN 1243 1244 ) ) ) 1245 1247 on on IN 1248 1251 the the DT 1252 1261 induction induction NN 1262 1264 of of IN 1265 1274 apoptosis apoptosis NN 1274 1275 . . . 1276 1288 Pretreatment Pretreatment NNP 1289 1291 of of IN 1292 1297 HL-60 HL-60 NNP 1298 1303 cells cell NNS 1304 1306 or or CC 1307 1317 thymocytes thymocyte NNS 1318 1322 with with IN 1323 1330 100-500 100-500 CD 1331 1337 microM microM NNP 1338 1340 OP OP NNP 1341 1344 for for IN 1345 1346 2 2 CD 1347 1349 hr hr NN 1349 1350 , , , 1351 1354 but but CC 1355 1358 not not RB 1359 1364 10-60 10-60 CD 1365 1367 mM mM NNP 1368 1371 NAC NAC NNP 1371 1372 , , , 1373 1383 suppressed suppress VBD 1384 1394 subsequent subsequent JJ 1395 1405 occurrence occurrence NN 1406 1408 of of IN 1409 1418 apoptosis apoptosis NN 1419 1426 induced induce VBN 1427 1429 by by IN 1430 1439 etoposide etoposide NN 1439 1440 . . . 1441 1446 These these DT 1447 1454 results result NNS 1455 1462 suggest suggest VBP 1463 1467 that that IN 1468 1471 the the DT 1472 1482 activation activation NN 1483 1485 of of IN 1486 1494 NF-kappa NF-kappa NNP 1495 1496 B B NNP 1497 1502 plays play VBZ 1503 1505 an an DT 1506 1515 important important JJ 1516 1520 role role NN 1521 1523 in in IN 1524 1527 the the DT 1528 1537 apoptotic apoptotic JJ 1538 1545 process process NN 1546 1548 of of IN 1549 1554 human human JJ 1555 1568 hematopoietic hematopoietic JJ 1569 1574 cells cell NNS 1574 1575 . . .