title: A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice.
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.
authors.affiliation: The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe Street, WBSB Room 406, Baltimore, MD 21205, USA.
authors.forename: Albena T
authors.initials: AT
authors.lastname: Dinkova-Kostova
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Jenkins
authors.forename: Scott L
authors.initials: SL
authors.lastname: Wehage
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Benedict
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Stephenson
authors.forename: Jed W
authors.initials: JW
authors.lastname: Fahey
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Karen T
authors.initials: KT
authors.lastname: Liby
authors.forename: Tadashi
authors.initials: T
authors.lastname: Honda
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Gribble
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
authors.forename: Paul
authors.initials: P
authors.lastname: Talalay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014315:Triterpenes / Q000008:administration & dosage*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D014315:Triterpenes; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D009252:NADPH Dehydrogenase