Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells

被引:139
作者
Chuang, SE
Yeh, PY
Lu, YS
Lai, GM
Liao, CM
Gao, M
Cheng, AL [1 ]
机构
[1] Natl Taiwan Univ, Coll Med, Ctr Canc Res, Taipei 10016, Taiwan
[2] Natl Hlth Res Inst, Div Canc Res, Taipei 11529, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Internal Med & Oncol, Taipei 10016, Taiwan
关键词
NF-kappa B; drug resistance; tamoxifen; curcumin; TPA; steroid;
D O I
10.1016/S0006-2952(02)00931-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Nuclear factor-kappaB (NF-kappaB) has been implicated in the development of drug resistance in cancer cells. We systematically examined the baseline levels of NF-kappaB activity of representative carcinoma cell lines, and the change of NF-kappaB activity in response to a challenge with four major anticancer drugs (doxorubicin, 5-fiuorouracil, cisplatin, and paclitaxel). We found that the basal level of NF-kappaB activity was heterogeneous and roughly correlated with drug resistance. When challenged with various drugs, all the cell lines examined responded with a transient activation of NF-kappaB which then declined to basal level despite variation in the concentration of the agent and the timing of the treatment. In contrast to tumor necrosis factor-alpha (TNF-alpha), which activates NF-kappaB in minutes, NF-kappaB activation induced by anticancer drugs usually occurred more than 1 hr after stimulation. A gradual increase of total NF-kappaB and its nuclear translocation, and cytoplasmic translocation of nuclear IkappaBalpha and its degradation were involved in this process. In particular, when cells were pretreated with common biologic modulators such as tamoxifen, dexamethasone, and curcumin, the doxorubicin-induced NF-kappaB activation was attenuated significantly. This inhibition may play a role in sensitizing cancer cells to chemotherapeutic drugs. This study has demonstrated that activation of NF-kappaB is a general cellular response to anticancer drugs, and the mechanism of activation appears to be distinct from that induced by TNF-alpha. These observations may have implications for improving the efficacy of systemic chemotherapy for cancer patients. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1709 / 1716
页数:8
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