A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

被引：15

作者：

Dinkova-Kostova, Albena T. ^{[1
,2
,3
]}

Jenkins, Stephanie N. ^{[1
]}

Wehage, Scott L. ^{[1
]}

Huso, David L. ^{[4
]}

Benedict, Andrea L. ^{[1
]}

Stephenson, Katherine K. ^{[1
]}

Fahey, Jed W. ^{[1
]}

Liu, Hua ^{[1
]}

Liby, Karen T. ^{[5
]}

Honda, Tadashi ^{[6
]}

Gribble, Gordon W. ^{[6
]}

Sporn, Michael B. ^{[5
]}

Talalay, Paul ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Lewis B & Dorothy Cullman Canc Chemoprotect Ctr, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Dept Med, Baltimore, MD 21205 USA

[3] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland

[4] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA

[5] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA

[6] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 04期

关键词：

2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile; Heme oxygenase 1; NQO1; SKH-1 hairless mouse;

D O I：

10.1016/j.bbrc.2008.01.026

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：

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：859 / 865

页数：7

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