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Chemopreventive Effects of Deguelin, a Novel Akt Inhibitor, on Tobacco-Induced Lung Tumorigenesis
Affiliations of authors: Departments of Thoracic/Head and Neck Medical Oncology (H-YL, S-HO, JKW, W-YK, HT, WKH), Imaging Physics (REP, DC), and Veterinary Medicine and Surgery (CSVP), The University of Texas M. D. Anderson Cancer Center, Houston, TX; Pharmacy Nursing Health Science, Purdue University, West Lafayette, IN (JMP); Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL (RMM)
Correspondence to: Ho-Young Lee, PhD, Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: hlee{at}mdanderson.org).
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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- Deguelin as a Chemopreventive Agent in Mouse Lung Tumorigenesis Induced by Tobacco Smoke Carcinogens
- Stephen S. Hecht
J Natl Cancer Inst 2005 97: 1634-1635.[Extract] [Full Text] [PDF]
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