Pro-apoptotic role of NF-κB:: Implications for cancer therapy

被引:106
作者
Radhakrishnan, Senthil K. [1 ]
Kamalakaran, Sitharthan
机构
[1] Univ Illinois, Dept Med Microbiol & Immunol, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2006年 / 1766卷 / 01期
关键词
NF-kappa B; apoptosis; cancer; drug target;
D O I
10.1016/j.bbcan.2006.02.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear factor-kappa B (NF-kappa B) is generally viewed as anti-apoptotic and oncogenic, leading to a quest for its inhibitors. However, recent evidence suggests that in some situations NF-kappa B may promote apoptosis. Depending on the specific cell type and the stimulus involved, NF-kappa B activation may lead to either anti- or pro-apoptotic response. Both these effects can be mediated by NF-kappa B in a context-dependent manner by selectively regulating its target genes. In this review, we discuss the evidence for NF-kappa B's pro-apoptotic role and explore the possible mechanisms behind it. We emphasize that rather than trying to inhibit NF-kappa B in cancer therapy, agents should be developed to unleash its pro-apoptotic ability. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:53 / 62
页数:10
相关论文
共 110 条
[1]   Induction of iNOS expression in skeletal muscle by IL-1β and NFκB activation:: an in vitro and in vivo study [J].
Adams, V ;
Nehrhoff, B ;
Späte, U ;
Linke, A ;
Schulze, PC ;
Baur, A ;
Gielen, S ;
Hambrecht, R ;
Schuler, G .
CARDIOVASCULAR RESEARCH, 2002, 54 (01) :95-104
[2]   Nuclear factor-κB modulates the p53 response in neurons exposed to DNA damage [J].
Aleyasin, H ;
Cregan, SP ;
Iyirhiaro, G ;
O'Hare, MJ ;
Callaghan, SM ;
Slack, RS ;
Park, DS .
JOURNAL OF NEUROSCIENCE, 2004, 24 (12) :2963-2973
[3]   cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-κB [J].
Anrather, J ;
Racchumi, G ;
Iadecola, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (01) :244-252
[4]   Evidence that activation of nuclear factor-κB is essential for the cytotoxic effects of doxorubicin and its analogues [J].
Ashikawa, K ;
Shishodia, S ;
Fokt, L ;
Priebe, W ;
Aggarwal, BB .
BIOCHEMICAL PHARMACOLOGY, 2004, 67 (02) :353-364
[5]   Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB [J].
Baldwin, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :241-246
[6]   Additive effect between NF-κB subunits and p53 protein for transcriptional activation of human p53 promoter [J].
Benoit, V ;
Hellin, AC ;
Huygen, S ;
Gielen, J ;
Bours, V ;
Merville, MP .
ONCOGENE, 2000, 19 (41) :4787-4794
[7]   The c-Rel transcription factor can both induce and inhibit apoptosis in the same cells via the upregulation of MnSOD [J].
Bernard, D ;
Monte, D ;
Vandenbunder, B ;
Abbadie, C .
ONCOGENE, 2002, 21 (28) :4392-4402
[8]   NF-κB activation mediates doxorubicin-induced cell death in N-type neuroblastoma cells [J].
Bian, X ;
McAllister-Lucas, LM ;
Shao, F ;
Schumacher, KR ;
Feng, ZW ;
Porter, AG ;
Castle, VP ;
Opipari, AW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (52) :48921-48929
[9]   p53 induces NF-κB activation by an IκB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1 [J].
Bohuslav, J ;
Chen, LF ;
Kwon, H ;
Mu, YJ ;
Greene, WC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (25) :26115-26125
[10]   Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines:: an absolute requirement for transcription factor NF-κB [J].
Bond, M ;
Fabunmi, RP ;
Baker, AH ;
Newby, AC .
FEBS LETTERS, 1998, 435 (01) :29-34