Anticarcinogenesis by dietary phytochemicals:: Cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-κB and AP-1 in abnormal cancer cells

被引:77
作者
Gopalakrishnan, Avanthika [1 ]
Kong, Ah-Ng Tony [1 ]
机构
[1] Rutgers State Univ, Ernest Mario Sch Pharm, Grad Program Pharmaceut Sci, Dept Pharmaceut, Piscataway, NJ 08854 USA
关键词
antioxidant response element; nuclear factor related factor 2; dietary phytochemicals; kelch-like ECH-associated protein (Keap1); activator protein 1; nuclear factor kappa B; caspases;
D O I
10.1016/j.fct.2007.09.082
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Cancer statistics from the American Cancer Society and other sources are a stark reminder of our failure to combat this deadly disease. Chemoprevention entails the use of specific naturally occurring dietary or synthetic agents to thwart cancer development and progression. Some of these agents are believed to do so by protecting the cells or tissues from the malicious attack of exogenous carcinogens and/or endogenous reactive oxygen/nitrogen species (RONS) by inducing several detoxifying/antioxidant enzymes that appear to form stable conjugates such as glutathione, glucuronides or sulfates thus rendering the carcinogenic species harmless. This process of inducing the cellular defense enzymes is believed to be mediated by the antioxidant response elements (ARE) within the promoter regions of these genes. Nrf2, a redox sensitive transcription factor has been documented to play a central role in ARE-driven gene expression. Nrf2, tinder normal unstimulated conditions, remains sequestered in the cytosol by Keap1. The putative chemopreventive agents disrupt the Nrf2-Keap1 association, thereby releasing Nrf2 which then translocates to the nucleus and drives the gene expression of detoxifying enzymes. The role of other transcription factors such as NF-kappa B and AP-1 in carcinogenesis is well established. By modulating the activity of these transcription factors and their upstream signaling molecules, naturally occurring dietary phytochemicals appear to cause apoptosis in abnormal cells that over-express these factors, thereby inhibiting the promotion and progression. This review discusses the most current and up to date understanding of the possible signaling mechanisms by which these naturally dietary phytochemicals can differentially modulate signal transduction cascades such that they can bring about apoptosis/cell death in abnormal cancer cells but at the same time induce defensive enzymes to protect against carcinogenesis in normal cells. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1257 / 1270
页数:14
相关论文
共 98 条
[1]   The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice [J].
Bachmeier, Beatrice E. ;
Nerlich, Andreas G. ;
Iancu, Cristina M. ;
Cilli, Michele ;
Schleicher, Erwin ;
Vene, Roberta ;
Dell'Eva, Raffaella ;
Jochum, Marianne ;
Albini, Adriana ;
Pfeffer, Ulrich .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2007, 19 (1-4) :137-152
[2]   Inflammation and cancer: back to Virchow? [J].
Balkwill, F ;
Mantovani, A .
LANCET, 2001, 357 (9255) :539-545
[3]   Curcurnin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element [J].
Balogun, E ;
Hoque, M ;
Gong, PF ;
Killeen, E ;
Green, CJ ;
Foresti, R ;
Alam, J ;
Motterlini, R .
BIOCHEMICAL JOURNAL, 2003, 371 :887-895
[4]   Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells [J].
Bhatia, N ;
Agarwal, C ;
Agarwal, R .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2001, 39 (02) :292-299
[5]   Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression [J].
Bloom, DA ;
Jaiswal, AK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (45) :44675-44682
[6]   Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells [J].
Chen, C ;
Shen, GX ;
Hebbar, V ;
Hu, R ;
Owuor, ED ;
Kong, ANT .
CARCINOGENESIS, 2003, 24 (08) :1369-1378
[7]   Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects [J].
Chen, C ;
Kong, ANT .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2005, 26 (06) :318-326
[8]   Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: Effect of chemical structure and stress signals [J].
Chen, C ;
Pung, D ;
Leong, V ;
Hebbar, V ;
Shen, GX ;
Nair, S ;
Li, W ;
Kong, ANT .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (10) :1578-1590
[9]   Dietary chemopreventive compounds and ARE/EpRE signaling [J].
Chen, C ;
Kong, ANT .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 36 (12) :1505-1516
[10]   Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism [J].
Chung, TW ;
Moon, SK ;
Chang, YC ;
Ko, JH ;
Lee, YC ;
Cho, G ;
Kim, SH ;
Kim, JG ;
Kim, CH .
FASEB JOURNAL, 2004, 18 (14) :1670-1681