Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis
- Authors
- Lee HY; Oh SH; Woo JK; Kim WY; Van Pelt CS; Price RE; Cody D; Tran H; Pezzuto JM; Moriarty RM; Hong WK
- Issue Date
- Nov-2005
- Publisher
- OXFORD UNIV PRESS INC
- Citation
- JOURNAL OF THE NATIONAL CANCER INSTITUTE, v.97, no.22, pp 1695 - 1699
- Pages
- 5
- Journal Title
- JOURNAL OF THE NATIONAL CANCER INSTITUTE
- Volume
- 97
- Number
- 22
- Start Page
- 1695
- End Page
- 1699
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/148717
- DOI
- 10.1093/jnci/dji377
- ISSN
- 0027-8874
1460-2105
- Abstract
- 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 AM 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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