The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice.

Published

Journal Article

We report the first use of new synthetic triterpenoids to prevent lung cancer in experimental animals. Female A/J mice were treated with the mutagenic carcinogen vinyl carbamate, which induces adenocarcinoma of the lung in all animals within 16 weeks. If mice were fed either the methyl ester or the ethyl amide derivative of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-ME and CDDO-EA, respectively), beginning 1 week after dosing with carcinogen, the number, size, and severity of lung carcinomas were markedly reduced. The mechanisms of action of CDDO-ME and CDDO-EA that are germane to these in vivo findings are the following results shown here in cell culture: (a) suppression of the ability of IFN-gamma to induce de novo formation of nitric oxide synthase in a macrophage-like cell line RAW264.7, (b) induction of heme oxygenase-1 in these RAW cells, and (c) suppression of phosphorylation of the transcription factor signal transducers and activators of transcription 3 as well as induction of apoptosis in human lung cancer cell lines.

Full Text

Duke Authors

Cited Authors

  • Liby, K; Royce, DB; Williams, CR; Risingsong, R; Yore, MM; Honda, T; Gribble, GW; Dmitrovsky, E; Sporn, TA; Sporn, MB

Published Date

  • March 15, 2007

Published In

Volume / Issue

  • 67 / 6

Start / End Page

  • 2414 - 2419

PubMed ID

  • 17363558

Pubmed Central ID

  • 17363558

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-06-4534

Language

  • eng

Conference Location

  • United States