Triptolide inhibits transcription factor NF-kappaB and induces apoptosis of multiple myeloma cells

被引:86
作者
Lou, YJ [1 ]
Jie, J [1 ]
Wang, YG [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Inst Hematol, Dept Hematol, Hangzhou 310003, Zhejiang, Peoples R China
关键词
triptolide; multiple myeloma; NF-kappaB; apoptosis; caspase; 3; PARP;
D O I
10.1016/j.leukres.2004.05.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Triptolide has been reported to be effective in the treatment of auto-immune diseases. This study investigates the cytotoxic function of triptolide on multiple myeloma (MM) cells. We found that triptolide inhibited the proliferation of both RPM18226 and U266 cells in a dose-dependent manner (10-80 ng/mL). Triptolide induced apoptosis in MM cells through activation of the cystein protease caspase 8, 9 and 3, and subsequent cleavage of the DNA repair enzyme poly (ADP-ribose) polymerase. Apoptosis was confirmed with cell-cycle analysis and annexin V staining. Moreover, triptolide down-regulated nuclear factor (NF)-kappaB activity in MM cell lines. In addition, triptolide also induced chemosensitivity to doxorubicin and suppressed cell proliferation of fresh MM cells. Therefore, triptolide appears to be a potent inducer of apoptosis in myeloma cells, and might have some benefit in the treatment of myeloma patients. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:99 / 105
页数:7
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