Journal Article

Chemopreventive Effects of Deguelin, a Novel Akt Inhibitor, on Tobacco-Induced Lung Tumorigenesis

Ho-Young Lee, Seung-Hyun Oh, Jong K. Woo, Woo-Young Kim, Carolyn S. Van Pelt, Roger E. Price, Dianna Cody, Hai Tran, John M. Pezzuto, Robert M. Moriarty and Waun Ki Hong

in JNCI: Journal of the National Cancer Institute

Volume 97, issue 22, pages 1695-1699
Published in print November 2005 | ISSN: 0027-8874
Published online November 2005 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/dji377
Chemopreventive Effects of Deguelin, a Novel Akt Inhibitor, on Tobacco-Induced Lung Tumorigenesis

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Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

Journal Article.  3986 words.  Illustrated.

Subjects: Medical Oncology

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