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

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

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Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.


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.

[Indexed for MEDLINE]

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