Abstract Title:

Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis.

Abstract Source:

J Natl Cancer Inst. 2005 Nov 16 ;97(22):1695-9. PMID: 16288123

Abstract Author(s):

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, Waun Ki Hong

Article Affiliation:

Ho-Young Lee


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.

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