A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis
Article first published online: 26 JUL 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 10, pages 2331–2339, 15 November 2007
How to Cite
Yasui, Y., Suzuki, R., Miyamoto, S., Tsukamoto, T., Sugie, S., Kohno, H. and Tanaka, T. (2007), A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis. Int. J. Cancer, 121: 2331–2339. doi: 10.1002/ijc.22976
- Issue published online: 25 SEP 2007
- Article first published online: 26 JUL 2007
- Manuscript Accepted: 6 JUN 2007
- Manuscript Received: 9 APR 2007
- Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research). Grant Numbers: 152052, 00120029, 18592076
- Kanazawa Medical University. Grant Numbers: H2006-6, C2006-3
- Ministry of Health, Labour and Welfare of Japan (Grant-in-Aid for Cancer Research and a Grant-in-Aid for the 3rd Term for a Comprehensive 10-year Strategy for Cancer Control)
- colon carcinogenesis;
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are known to modulate carcinogenesis. In this study, we investigated whether a lipophilic HMG-CoA reductase inhibitor pitavastatin suppresses inflammation-related mouse colon carcinogenesis. Male CD-1 (ICR) mice were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 2% (w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. The experimental diets containing pitavastatin at 2 dose levels (1 and 10 ppm) were fed to male CD-1 (ICR) mice for 17 weeks, staring 1 week after the cessation of DSS exposure. The effects of dietary pitavastatin on colonic tumor development were assessed at Weeks 5, 10 and 20. Feeding with pitavastatin at both doses significantly inhibited the multiplicity of colonic adenocarcinoma at Week 20. Furthermore, the treatment significantly lowered the positive rates of proliferating cell nuclear antigen and increased the apoptotic index in the colonic epithelial malignancies. The treatment also reduced nitrotyrosine-positivity in the colonic mucosa. Our findings thus show that pitavastatin is effective in inhibiting colitis-related colon carcinogenesis through modulation of mucosal inflammation, oxidative/nitrosative stress, and cell proliferation. © 2007 Wiley-Liss, Inc.