Molecular mechanisms of cancer prevention by selenium compounds

被引:94
作者
Fleming, J [1 ]
Ghose, A [1 ]
Harrison, PR [1 ]
机构
[1] Beatson Inst Canc Res, CRC, Beatson Labs, Glasgow G61 1BD, Lanark, Scotland
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 2001年 / 40卷 / 01期
关键词
D O I
10.1207/S15327914NC401_9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Selenium compounds that are chemopreventive in animal models inhibit cell growth and induce apoptosis in vitro, and this could explain how they reduce the outgrowth of tumor cells in vivo. Our recent work has shown that primary cultures of oral carcinoma biopsies are significantly more sensitive than normal oral mucosa cultures to induction of apoptosis by a natural selenium metabolite [selenodiglutathione (SDG)], and this is associated with induction of Fas ligand, a well-known mediator of apoptosis in other contexts, and activation of so-called stress kinase signaling pathways, particularly the Jun NH2-terminal kinase (JNK). Heme oxygenase, another marker of stress responses, is also induced by selenite and SDG. The selective activation of the Fas pathway in carcinomas could be responsible directly for their destruction by apoptosis or target them for attack by immunologic responses. In contrast, although the potent pharmacological selenium chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC) also induces Fas ligand, heme oxygenase, and stress kinase pathways, apoptosis/Fas induction is not so strongly JNK-dependent and p-XSC does not show tumor selectivity. These differences in mechanism between SDG and p-XSC may be due to the manner in which they induce redox changes in the cells, since although the effects of SDG and p-XSC are prevented by antioxidants such as glutathione or N-acetylcysteine, hydroxyl radical scavengers such as mannitol or pyrrolidine dithiocarbamate only protect against the effects of p-XSC.
引用
收藏
页码:42 / 49
页数:8
相关论文
共 89 条
[1]   alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Effects of base-line characteristics and study compliance [J].
Albanes, D ;
Heinonen, OP ;
Taylor, PR ;
Virtamo, J ;
Edwards, BK ;
Rautalahti, M ;
Hartman, AM ;
Palmgren, J ;
Freedman, LS ;
Haapakoski, J ;
Barrett, MJ ;
Pietinen, P ;
Malila, N ;
Tala, E ;
Liippo, K ;
Salomaa, ER ;
Tangrea, JA ;
Teppo, L ;
Askin, FB ;
Taskinen, E ;
Erozan, Y ;
Greenwald, P ;
Huttunen, JK .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1996, 88 (21) :1560-1570
[2]  
Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group, 1994, N Engl J Med, V330, P1029, DOI 10.1056/NEJM199404143301501
[3]   TISSUE-SPECIFIC REGULATION OF SELENOENZYME GENE-EXPRESSION DURING SELENIUM DEFICIENCY IN RATS [J].
BERMANO, G ;
NICOL, F ;
DYER, JA ;
SUNDE, RA ;
BECKETT, GJ ;
ARTHUR, JR ;
HESKETH, JE .
BIOCHEMICAL JOURNAL, 1995, 311 :425-430
[4]  
BJORNSTEDT M, 1992, J BIOL CHEM, V267, P8030
[5]   NUTRITION INTERVENTION TRIALS IN LINXIAN, CHINA - SUPPLEMENTATION WITH SPECIFIC VITAMIN MINERAL COMBINATIONS, CANCER INCIDENCE, AND DISEASE-SPECIFIC MORTALITY IN THE GENERAL-POPULATION [J].
BLOT, WJ ;
LI, JY ;
TAYLOR, PR ;
GUO, WD ;
DAWSEY, S ;
WANG, GQ ;
YANG, CS ;
ZHENG, SF ;
GAIL, M ;
LI, GY ;
YU, Y ;
LIU, BQ ;
TANGREA, J ;
SUN, YH ;
LIU, FS ;
FRAUMENI, JF ;
ZHANG, YH ;
LI, B .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (18) :1483-1492
[6]   RESPONSE OF RAT SELENOPROTEIN-P TO SELENIUM ADMINISTRATION AND FATE OF ITS SELENIUM [J].
BURK, RF ;
HILL, KE ;
READ, R ;
BELLEW, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (01) :E26-E30
[7]   ALLIUM CHEMISTRY - IDENTIFICATION OF SELENOAMINO ACIDS IN ORDINARY AND SELENIUM-ENRICHED GARLIC, ONION, AND BROCCOLI USING GAS-CHROMATOGRAPHY WITH ATOMIC-EMISSION DETECTION [J].
CAI, XJ ;
BLOCK, E ;
UDEN, PC ;
ZHANG, X ;
QUIMBY, BD ;
SULLIVAN, JJ .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 1995, 43 (07) :1754-1757
[8]   Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues [J].
Cheng, WH ;
Ho, YS ;
Ross, DA ;
Valentine, BA ;
Combs, GF ;
Lei, XG .
JOURNAL OF NUTRITION, 1997, 127 (08) :1445-1450
[9]  
Clark LC, 1998, BRIT J UROL, V81, P730
[10]   Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin a randomized controlled trial - A randomized controlled trial [J].
Clark, LC ;
Combs, GF ;
Turnbull, BW ;
Slate, EH ;
Chalker, DK ;
Chow, J ;
Davis, LS ;
Glover, RA ;
Graham, GF ;
Gross, EG ;
Krongrad, A ;
Lesher, JL ;
Park, HK ;
Sanders, BB ;
Smith, CL ;
Taylor, JR .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (24) :1957-1963