A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis
(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)
- author
- Sido, Abigail ; Radhakrishnan, Sridhar ; Kim, Sung Woo ; Eriksson, Elisabeth LU ; Shen, Frank ; Li, Qunhua ; Bhat, Vadiraja ; Reddivari, Lavanya and Vanamala, Jairam K P
- organization
- publishing date
- 2017-05-01
- 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
- pmid:28193578
- 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
- 2024-03-31 03:13:44
@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}},
keywords = {{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}},
doi = {{10.1016/j.jnutbio.2017.01.012}},
volume = {{43}},
year = {{2017}},
}