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. 2008 Mar 21;367(4):859-65.
doi: 10.1016/j.bbrc.2008.01.026. Epub 2008 Jan 17.

A Dicyanotriterpenoid Induces Cytoprotective Enzymes and Reduces Multiplicity of Skin Tumors in UV-irradiated Mice

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A Dicyanotriterpenoid Induces Cytoprotective Enzymes and Reduces Multiplicity of Skin Tumors in UV-irradiated Mice

Albena T Dinkova-Kostova et al. Biochem Biophys Res Commun. .

Abstract

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(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.

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