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

作者：Dinkova Kostova Albena T; Jenkins Stephanie N; Wehage Scott L; Huso David L; Benedict Andrea L; Stephenson Katherine K; Fahey Jed W; Liu Hua; Liby Karen T; Honda Tadashi; Gribble Gordon W; S**** Michael B; Talalay Paul^*

来源：Biochemical and Biophysical Research Communications, 2008, 367(4): 859-865.

DOI：10.1016/j.bbrc.2008.01.026

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

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.

• 出版日期2008-3-21