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A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis.

J. Nutr. Biochem.2017 May;43:11-17. Epub 2017 Jan 28
Abigail Sido 1 , Sridhar Radhakrishnan 1 , Sung Woo Kim 2 , Elisabeth Eriksson 3 , Frank Shen 4 , Qunhua Li 5 , Vadiraja Bhat 5 , Lavanya Reddivari 6 , Jairam K P Vanamala 7
Abigail Sido 1 , Sridhar Radhakrishnan 1 , Sung Woo Kim 2 , Elisabeth Eriksson 3 , Frank Shen 4 , Qunhua Li 5 , Vadiraja Bhat 5 , Lavanya Reddivari 6 , Jairam K P Vanamala 7
+ et al

[No authors listed]

Author information
  • 1 Department of Food Science, The Pennsylvania State University, University Park, PA, USA.
  • 2 Department of Animal Science, North Carolina State University, Raleigh, North Carolina, USA.
  • 3 Department of Biotechnology, Lund University, Lund, Sweden.
  • 4 Department of Statistics, The Pennsylvania State University, University Park, PA, USA.
  • 5 Agilent Technologies, Wilmington, DE, USA.
  • 6 Department of Plant Science, The Pennsylvania State University, University Park, PA, USA.
  • 7 Department of Food Science, The Pennsylvania State University, University Park, PA, USA; The Pennsylvania State University Milton S. Hershey College of Medicine, Hershey, PA, USA; Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, PA, USA. Electronic address: juv4@psu.edu.

摘要


Studies have shown a causal link between high-calorie diet (HCD) and colon cancer. However, molecular mechanisms are not fully elucidated. To understand etiology of HCD-induced colon carcinogenesis, we screened 10 pathways linked to elevated colonic cell proliferation and chronic inflammation in an HCD-consuming human-relevant pig model. We observed elevated colonic mucosal interleukin-6 (IL-6) expression in HCD-consuming pigs compared to standard diet controls (SD, P=.04), and IL-6 strongly correlated with Ki-67 proliferative index and zone, early biomarkers of colon cancer risk (r=0.604 and 0.743 and P=.017 and .002, respectively). Liquid chromatography-tandem mass spectrometry-based proteomic analysis and Ingenuity Pathway Analysis showed that HCD consumption altered IL-6 signaling pathway proteins (PI3KR4, IL-1α, Mapk10, Akt3, PIK3CG, PIK3R5, Map2k2). Furthermore, these proteins also correlated with Ki-67 proliferative index/zone. Anti-IL-6 therapeutics are available for treating colon cancer; however, they are expensive and induce negative side effects. Thus, whole foods could be a better way to combat low-grade chronic colonic inflammation and colon cancer. Whole plant foods have been shown to decrease chronic diseases due to the potential of anti-inflammatory dietary compounds acting synergistically. We observed that supplementation of HCD with anthocyanin-containing purple-fleshed potatoes (10% w/w), even after baking, suppressed HCD-induced IL-6 expression (P=.03) and the IL-6-related proteins IL-1α and Map2k1 (P≤.1). Our results highlight the importance of IL-6 signaling in diet-linked induction/prevention of colonic inflammation/cancer and demonstrate the potential of a food-based approach to target IL-6 signaling.

KEYWORDS: Colon cancer, Colonic inflammation, High-calorie diet, Interleukin-6, Pig model, Purple-fleshed potatoes