0 5 Bcl-2 bcl-2 NN 6 13 protein protein NN 14 22 inhibits inhibit VBZ 23 38 bufalin-induced bufalin-induced JJ 39 48 apoptosis apoptosis NN 49 56 through through IN 57 67 inhibition inhibition NN 68 70 of of IN 71 88 mitogen-activated mitogen-activated JJ 89 96 protein protein NN 97 103 kinase kinase NNP 104 114 activation activation NN 115 117 in in IN 118 123 human human JJ 124 132 leukemia leukemia NN 133 137 U937 u937 NN 138 143 cells cell NNS 143 144 . . . 146 148 In in IN 149 150 a a DT 151 159 previous previous JJ 160 165 study study NN 165 166 , , , 167 169 we we PRP 170 182 demonstrated demonstrate VBD 183 187 that that IN 188 195 bufalin bufalin NN 195 196 , , , 197 202 which which WDT 203 205 is be VBZ 206 208 an an DT 209 215 active active JJ 216 225 principle principle NN 226 228 of of IN 229 236 Chinese chinese JJ 237 245 medicine medicine NN 245 246 , , , 247 254 chan’su chan'su NN 254 255 , , , 256 262 caused cause VBD 263 272 apoptosis apoptosis NN 273 275 in in IN 276 281 human human JJ 282 290 leukemia leukemia NN 291 295 U937 u937 NN 296 301 cells cell NNS 302 304 by by IN 305 314 anomalous anomalous JJ 315 325 activation activation NN 326 328 of of IN 329 346 mitogen-activated mitogen-activated JJ 347 354 protein protein NN 355 361 kinase kinase NNP 362 363 ( ( ( 363 367 MAPK MAPK NNP 367 368 ) ) ) 369 372 via via IN 373 376 the the DT 377 386 signaling signaling NN 387 394 pathway pathway NN 395 397 of of IN 398 401 Ras Ras NNP 401 402 , , , 403 408 Raf-1 Raf-1 NNP 408 409 , , , 410 413 and and CC 414 418 MAPK MAPK NNP 419 427 kinase-1 kinase-1 NN 427 428 . . . 429 433 Here here RB 433 434 , , , 435 437 we we PRP 438 444 report report VBP 445 448 the the DT 449 455 effect effect NN 456 458 of of IN 459 473 overexpression overexpression NN 474 476 of of IN 477 482 bcl-2 bcl-2 NN 483 485 in in IN 486 490 U937 u937 NN 491 496 cells cell NNS 497 499 on on IN 500 503 the the DT 504 513 signaling signaling NN 514 521 pathway pathway NN 522 524 of of IN 525 534 apoptosis apoptosis NN 535 539 that that WDT 540 542 is be VBZ 543 550 induced induce VBN 551 553 by by IN 554 561 bufalin bufalin NN 561 562 . . . 563 566 The the DT 567 574 results result NNS 575 584 indicated indicate VBD 585 589 that that IN 590 593 the the DT 594 603 apoptosis apoptosis NN 604 611 induced induce VBN 612 614 by by IN 615 622 bufalin bufalin NN 623 625 in in IN 626 630 U937 u937 NN 631 636 cells cell NNS 637 640 was be VBD 641 654 significantly significantly RB 655 664 inhibited inhibit VBN 665 667 by by IN 668 682 overexpression overexpression NN 683 685 of of IN 686 689 the the DT 690 695 Bcl-2 bcl-2 NN 696 703 protein protein NN 703 704 . . . 705 707 No no DT 708 719 significant significant JJ 720 730 difference difference NN 731 734 was be VBD 735 743 detected detect VBN 744 746 in in IN 747 750 the the DT 751 761 activation activation NN 762 764 of of IN 765 769 MAPK MAPK NNP 770 778 kinase-1 kinase-1 NN 779 783 that that WDT 784 786 is be VBZ 787 794 induced induce VBN 795 797 by by IN 798 805 bufalin bufalin NN 806 808 in in IN 809 818 wild-type wild-type JJ 819 821 or or CC 822 841 Bcl-2-overexpressed bcl-2-overexpressed JJ 842 846 U937 u937 NN 847 852 cells cell NNS 852 853 ; ; : 854 861 however however RB 861 862 , , , 863 866 the the DT 867 877 activation activation NN 878 880 of of IN 881 885 MAPK MAPK NNP 886 888 by by IN 889 896 bufalin bufalin NN 897 900 was be VBD 901 914 significantly significantly RB 915 925 attenuated attenuate VBN 926 928 in in IN 929 932 the the DT 933 938 cells cell NNS 939 953 overexpressing overexpresse VBG 954 959 Bcl-2 bcl-2 NN 959 960 . . . 961 968 Bufalin Bufalin NNP 969 978 treatment treatment NN 979 988 activated activate VBD 989 998 activator activator NN 999 1008 protein-1 protein-1 NN 1009 1024 transcriptional transcriptional JJ 1025 1033 activity activity NN 1033 1034 ; ; : 1035 1042 however however RB 1042 1043 , , , 1044 1048 this this DT 1049 1059 activation activation NN 1060 1063 was be VBD 1064 1073 decreased decrease VBN 1074 1076 to to TO 1077 1079 40 40 CD 1079 1080 % % NN 1081 1083 in in IN 1084 1103 bcl-2-overexpressed bcl-2-overexpressed JJ 1104 1108 U937 u937 NN 1109 1114 cells cell NNS 1114 1115 . . . 1116 1121 These these DT 1122 1129 results result NNS 1130 1138 indicate indicate VBP 1139 1143 that that IN 1144 1149 Bcl-2 bcl-2 NN 1150 1154 acts act VBZ 1155 1165 downstream downstream RB 1166 1168 of of IN 1169 1173 MAPK MAPK NNP 1174 1182 kinase-1 kinase-1 NN 1183 1186 but but CC 1187 1195 upstream upstream RB 1196 1198 of of IN 1199 1203 MAPK MAPK NNP 1204 1207 and and CC 1208 1215 suggest suggest VBP 1216 1220 that that IN 1220 1221 , , , 1222 1224 in in IN 1225 1228 the the DT 1229 1238 signaling signaling NN 1239 1246 pathway pathway NN 1247 1249 of of IN 1250 1253 the the DT 1254 1263 apoptotic apoptotic JJ 1264 1271 process process NN 1272 1279 induced induce VBN 1280 1282 by by IN 1283 1290 bufalin bufalin NN 1290 1291 , , , 1292 1295 the the DT 1296 1311 transcriptional transcriptional JJ 1312 1320 activity activity NN 1321 1323 of of IN 1324 1333 activator activator NN 1334 1343 protein-1 protein-1 NN 1344 1347 may may MD 1348 1350 be be VB 1351 1365 down-regulated down-regulate VBN 1366 1373 through through IN 1374 1377 the the DT 1378 1388 inhibition inhibition NN 1389 1391 of of IN 1392 1396 MAPK MAPK NNP 1397 1405 activity activity NN 1406 1408 by by IN 1409 1414 Bcl-2 bcl-2 NN 1414 1415 . . .