Advanced

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

Sido, Abigail; Radhakrishnan, Sridhar; Kim, Sung Woo; Eriksson, Elisabeth LU ; Shen, Frank; Li, Qunhua; Bhat, Vadiraja; Reddivari, Lavanya and Vanamala, Jairam K P (2017) In Journal of Nutritional Biochemistry 43. p.11-17
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Colon cancer, Colonic inflammation, High-calorie diet, Interleukin-6, Pig model, Purple-fleshed potatoes
in
Journal of Nutritional Biochemistry
volume
43
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:85012031557
ISSN
0955-2863
DOI
10.1016/j.jnutbio.2017.01.012
language
English
LU publication?
yes
id
a638b160-b484-49cf-abf4-b1e7881ad25d
date added to LUP
2017-02-27 08:23:28
date last changed
2018-03-25 04:34:41
@article{a638b160-b484-49cf-abf4-b1e7881ad25d,
  abstract     = {<p>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.</p>},
  author       = {Sido, Abigail and Radhakrishnan, Sridhar and Kim, Sung Woo and Eriksson, Elisabeth and Shen, Frank and Li, Qunhua and Bhat, Vadiraja and Reddivari, Lavanya and Vanamala, Jairam K P},
  issn         = {0955-2863},
  keyword      = {Colon cancer,Colonic inflammation,High-calorie diet,Interleukin-6,Pig model,Purple-fleshed potatoes},
  language     = {eng},
  month        = {05},
  pages        = {11--17},
  publisher    = {Elsevier},
  series       = {Journal of Nutritional Biochemistry},
  title        = {A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis},
  url          = {http://dx.doi.org/10.1016/j.jnutbio.2017.01.012},
  volume       = {43},
  year         = {2017},
}