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

Albena T. Dinkova-Kostova, Stephanie N. Jenkins, Scott L. Wehage, David L. Huso, Andrea L. Benedict, Katherine K. Stephenson, Jed W. Fahey, Hua Liu, Karen T. Liby, Tadashi Honda, Gordon W. Gribble, Michael B. Sporn, Paul Talalay

Research output: Contribution to journalArticlepeer-review

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/cm2/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.

Original languageEnglish (US)
Pages (from-to)859-865
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number4
DOIs
StatePublished - Mar 21 2008

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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