Nuclear factor-κB, cancer, and apoptosis

被引:195
作者
Bours, V [1 ]
Bentires-Alj, M [1 ]
Hellin, AC [1 ]
Viatour, P [1 ]
Robe, P [1 ]
Delhalle, S [1 ]
Benoit, V [1 ]
Merville, MP [1 ]
机构
[1] Univ Liege, Lab Med Chem & Med Oncol, B-4000 Liege, Belgium
关键词
apoptosis; cancer; transcription factors; NF-kappa B;
D O I
10.1016/S0006-2952(00)00391-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The rule of nuclear factor (NF)-kappa B in the regulation of apoptosis in normal and cancer cells has been extensively studied in recent years. Constitutive NF-kappa B activity in B lymphocytes as well as in Hodgkin's disease and breast cancer cells protects these cells against apoptosis. It has also been reported that NF-kappa B activation by tumor necrosis factor (TNF)-alpha, chemotherapeutic drugs, or ionizing radiations can protect several cell types against apoptosis, suggesting that NF-kappa B could participate in resistance to cancer treatment. These observations were explained by the regulation of antiapoptotic gene expression by NF-kappa B. However, in our experience, inhibition of NF-kappa B activity in several cancer cell lines has a very variable effect on cell mortality, depending on the cell type, the stimulus, and the level of NF-kappa B inhibition. Moreover, in some experimental systems, NF-kappa B activation is required for the onset of apoptosis. Therefore, it is likely that the NF-kappa B antiapoptotic role in response to chemotherapy is cell type- and signal-dependent and that the level of NF-kappa B inhibition is important. These issues will have to be carefully investigated before considering NF-kappa B as a target for genetic or pharmacological anticancer therapies. BIOCHEM PHARMACOL 60;8:1085-1090, 2000. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:1085 / 1089
页数:5
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