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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Abigail Sido
  • Sridhar Radhakrishnan
  • Sung Woo Kim
  • Elisabeth Eriksson
  • Frank Shen
  • Qunhua Li
  • Vadiraja Bhat
  • Lavanya Reddivari
  • Jairam K P Vanamala
Enheter & grupper
Externa organisationer
  • Pennsylvania State University
  • North Carolina State University
  • Agilent Technologies
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Läkemedelskemi
  • Näringslära

Nyckelord

Originalspråkengelska
Sidor (från-till)11-17
Antal sidor7
TidskriftJournal of Nutritional Biochemistry
Volym43
StatusPublished - 2017 maj 1
PublikationskategoriForskning
Peer review utfördJa