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Zerumbone, a tropical ginger sesquiterpene, inhibits colon and lung carcinogenesis in mice
Article first published online: 11 NOV 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 2, pages 264–271, 15 January 2009
How to Cite
Kim, M., Miyamoto, S., Yasui, Y., Oyama, T., Murakami, A. and Tanaka, T. (2009), Zerumbone, a tropical ginger sesquiterpene, inhibits colon and lung carcinogenesis in mice. Int. J. Cancer, 124: 264–271. doi: 10.1002/ijc.23923
- Issue published online: 14 NOV 2008
- Article first published online: 11 NOV 2008
- Manuscript Accepted: 30 JUL 2008
- Manuscript Received: 15 JUN 2008
- Cancer Research, for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan
- Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Grant Numbers: 8592076, 7015016, 18880030
- Project Research from the High-Technology Center of Kanazawa Medical University. Grant Numbers: H2007-12, S2006-9
Zerumbone (ZER), present in subtropical ginger Zingiber zerumbet Smith, possesses anti-growth and anti-inflammatory properties in several human cancer cell lines. ZER also down-regulates the cyclooxygenase-2 and inducible nitric oxide synthase expression via modulation of nuclear factor (NF)-κB activation in cell culture systems. These findings led us to investigate whether ZER is able to inhibit carcinogenesis in the colon and lung, using 2 different preclinical mouse models. In Exp. 1, a total of 85 male ICR mice were initiated using a single intraperitoneal (i.p.) injection with azoxymethane (AOM, 10 mg/kg bw) and promoted by 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days for rapid induction of colonic neoplasms. Animals were then fed the diet containing 100, 250 or 500 ppm ZER for 17 weeks. In Exp. 2, a total of 50 female A/J mice were given a single i.p. injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (10 μmol/mouse) to induce lung proliferative lesions. They were then fed the diet mixed with 100, 250 or 500 ppm ZER for 21 weeks. At the termination of the experiments (wk 20 of Exp. 1 and wk 22 of Exp. 2), all animals were subjected to complete necropsy examination to determine the pathological lesions in both tissues. Oral administration of ZER at 100, 250 and 500 ppm significantly inhibited the multiplicity of colonic adenocarcinomas. The treatment also suppressed colonic inflammation. In the lung carcinogenesis, ZER feeding at 250 and 500 ppm significantly inhibited the multiplicity of lung adenomas in a dose-dependent manner. Feeding with ZER resulted in inhibition of proliferation, induction of apoptosis, and suppression of NFκB and heme oxygenase (HO)-1 expression in tumors developed in both tissues. Our findings suggest that dietary administration of ZER effectively suppresses mouse colon and lung carcinogenesis through multiple modulatory mechanisms of growth, apoptosis, inflammation and expression of NFκB and HO-1 that are involved in carcinogenesis in the colon and lung. © 2008 Wiley-Liss, Inc.