Abstract
Abstract Obesity and related metabolic abnormalities, including a state of chronic inflammation and oxidative stress, are risk factors for colon cancer. Dysregulation the renin-angiotensin system (RAS) also plays a critical role in obesity-related metabolic disorders and certain types of carcinogenesis. In the present study, we examined the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB), both of which target RAS, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) and then they received drinking water containing captopril (ACE inhibitor, 5 mg/kg/day) or telmisartan (ARB, 5 mg/kg/day) for 7 weeks. At sacrifice, administration of captopril and telmisartan significantly reduced the total number of colonic premalignant lesions, aberrant crypt foci and β-catenin accumulated crypts, compared with the control untreated-group. Both agents decreased the expression levels of TNF-α mRNA on the colonic mucosa of experimental mice. The expression levels of TNF-α, COX-2, IL-1β, IL-6, and PAI-1 mRNAs on the visceral fat were also decreased by administration of these agents. In addition, captopril and telmisartan significantly decreased the levels of urinary 8-OHdG, a surrogate marker of oxidative damage to DNA, in the experimental mice. These findings suggest that both ACE inhibitor and ARB suppress obesity-related colon carcinogenesis by attenuating chronic inflammation and reducing oxidative stress. Targeting the dysregulation of RAS might be, therefore, one of the effective strategies for the chemoprevention of obesity-related colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 830. doi:10.1158/1538-7445.AM2011-830
Published Version
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