Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway

Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells...

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Main Authors: Saadatdoust, Z., Pandurangan, A.K., Sadagopan, S.K.A., Esa, N.M., Ismail, A., Mustafa, Mohd Rais
Format: Article
Published: 2015
Subjects:
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author Saadatdoust, Z.
Pandurangan, A.K.
Sadagopan, S.K.A.
Esa, N.M.
Ismail, A.
Mustafa, Mohd Rais
author_facet Saadatdoust, Z.
Pandurangan, A.K.
Sadagopan, S.K.A.
Esa, N.M.
Ismail, A.
Mustafa, Mohd Rais
author_sort Saadatdoust, Z.
collection UM
description Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells and play an important role in the pathogenesis of IBD and CRC. Cocoa is enriched with polyphenols that known to possess antioxidant, anti-inflammatory and antitumor activities. Here, we explored the antitumor effects and mechanisms of cocoa diet on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium model, with a particular focus on whether cocoa exerts its anticancer effect through the IL-6/STAT3 pathway. We found that cocoa significantly decreased the tumor incidence and size in CAC-induced mice. In addition to inhibiting proliferation of tumor epithelial cells, cocoa suppressed colonic IL-6 expression and subsequently activation of STAT3. Thus, our findings demonstrated that cocoa diet suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation. In addition, cocoa induces apoptosis by increased the expressions of Bax and caspase 3 and decreased Bcl-xl. Thus, we conclude that cocoa may be a potential agent in the prevention and treatment of CAC. (C) 2015 Elsevier Inc. All rights reserved.
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spelling um.eprints-164512019-12-18T06:50:00Z http://eprints.um.edu.my/16451/ Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway Saadatdoust, Z. Pandurangan, A.K. Sadagopan, S.K.A. Esa, N.M. Ismail, A. Mustafa, Mohd Rais Q Science (General) QD Chemistry Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells and play an important role in the pathogenesis of IBD and CRC. Cocoa is enriched with polyphenols that known to possess antioxidant, anti-inflammatory and antitumor activities. Here, we explored the antitumor effects and mechanisms of cocoa diet on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium model, with a particular focus on whether cocoa exerts its anticancer effect through the IL-6/STAT3 pathway. We found that cocoa significantly decreased the tumor incidence and size in CAC-induced mice. In addition to inhibiting proliferation of tumor epithelial cells, cocoa suppressed colonic IL-6 expression and subsequently activation of STAT3. Thus, our findings demonstrated that cocoa diet suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation. In addition, cocoa induces apoptosis by increased the expressions of Bax and caspase 3 and decreased Bcl-xl. Thus, we conclude that cocoa may be a potential agent in the prevention and treatment of CAC. (C) 2015 Elsevier Inc. All rights reserved. 2015 Article PeerReviewed Saadatdoust, Z. and Pandurangan, A.K. and Sadagopan, S.K.A. and Esa, N.M. and Ismail, A. and Mustafa, Mohd Rais (2015) Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway. Journal of Nutritional Biochemistry, 26 (12). pp. 1547-1558. ISSN 0955-2863, DOI https://doi.org/10.1016/j.jnutbio.2015.07.024 <https://doi.org/10.1016/j.jnutbio.2015.07.024>. https://doi.org/10.1016/j.jnutbio.2015.07.024 doi:10.1016/j.jnutbio.2015.07.024
spellingShingle Q Science (General)
QD Chemistry
Saadatdoust, Z.
Pandurangan, A.K.
Sadagopan, S.K.A.
Esa, N.M.
Ismail, A.
Mustafa, Mohd Rais
Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title_full Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title_fullStr Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title_full_unstemmed Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title_short Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
title_sort dietary cocoa inhibits colitis associated cancer a crucial involvement of the il 6 stat3 pathway
topic Q Science (General)
QD Chemistry
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