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Cancer Prevention Research
Cancer Prevention Research
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Research Article

Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis

Xiangli Cui, Yu Jin, Anne B. Hofseth, Edsel Pena, Joshua Habiger, Alexander Chumanevich, Deepak Poudyal, Mitzi Nagarkatti, Prakash S. Nagarkatti, Udai P. Singh and Lorne J. Hofseth
Xiangli Cui
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Yu Jin
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Anne B. Hofseth
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Edsel Pena
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Joshua Habiger
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Alexander Chumanevich
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Deepak Poudyal
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Mitzi Nagarkatti
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Prakash S. Nagarkatti
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Udai P. Singh
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Lorne J. Hofseth
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DOI: 10.1158/1940-6207.CAPR-09-0117 Published April 2010
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Abstract

Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects, including anti-inflammatory, cardio-protective, and cancer-protective activities. It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders. Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon associated with a high colon cancer risk. Here, we used a dextran sulfate sodium (DSS) mouse model of colitis, which resembles human ulcerative colitis pathology. Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner. Resveratrol significantly improves inflammation score, downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria, and modulates CD3+ T cells that express tumor necrosis factor-α and IFN-γ. Markers of inflammation and inflammatory stress (p53 and p53-phospho-Ser15) are also downregulated by resveratrol. Because chronic colitis drives colon cancer risk, we carried out experiments to determine the chemopreventive properties of resveratrol. Tumor incidence is reduced from 80% in mice treated with azoxymethane (AOM) + DSS to 20% in mice treated with AOM + DSS + resveratrol (300 ppm). Tumor multiplicity also decreased with resveratrol treatment. AOM + DSS–treated mice had 2.4 ± 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol, which had 0.2 ± 0.13 tumors per animal. The current study indicates that resveratrol is a useful, nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis. Cancer Prev Res; 3(4); 549–59. ©2010 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Received June 12, 2009.
  • Revision received November 6, 2009.
  • Accepted November 16, 2009.
  • ©2010 American Association for Cancer Research.
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Cancer Prevention Research: 3 (4)
April 2010
Volume 3, Issue 4
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Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis
Xiangli Cui, Yu Jin, Anne B. Hofseth, Edsel Pena, Joshua Habiger, Alexander Chumanevich, Deepak Poudyal, Mitzi Nagarkatti, Prakash S. Nagarkatti, Udai P. Singh and Lorne J. Hofseth
Cancer Prev Res April 1 2010 (3) (4) 549-559; DOI: 10.1158/1940-6207.CAPR-09-0117

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Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis
Xiangli Cui, Yu Jin, Anne B. Hofseth, Edsel Pena, Joshua Habiger, Alexander Chumanevich, Deepak Poudyal, Mitzi Nagarkatti, Prakash S. Nagarkatti, Udai P. Singh and Lorne J. Hofseth
Cancer Prev Res April 1 2010 (3) (4) 549-559; DOI: 10.1158/1940-6207.CAPR-09-0117
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