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

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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; Shen, Frank; Li, Qunhua; Bhat, Vadiraja; Reddivari, Lavanya; Vanamala, Jairam K P.

In: Journal of Nutritional Biochemistry, Vol. 43, 01.05.2017, p. 11-17.

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Sido, Abigail ; Radhakrishnan, Sridhar ; Kim, Sung Woo ; Eriksson, Elisabeth ; Shen, Frank ; Li, Qunhua ; Bhat, Vadiraja ; Reddivari, Lavanya ; Vanamala, Jairam K P. / A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis. In: Journal of Nutritional Biochemistry. 2017 ; Vol. 43. pp. 11-17.

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TY - JOUR

T1 - A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis

AU - Sido, Abigail

AU - Radhakrishnan, Sridhar

AU - Kim, Sung Woo

AU - Eriksson, Elisabeth

AU - Shen, Frank

AU - Li, Qunhua

AU - Bhat, Vadiraja

AU - Reddivari, Lavanya

AU - Vanamala, Jairam K P

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

KW - Colon cancer

KW - Colonic inflammation

KW - High-calorie diet

KW - Interleukin-6

KW - Pig model

KW - Purple-fleshed potatoes

UR - http://www.scopus.com/inward/record.url?scp=85012031557&partnerID=8YFLogxK

U2 - 10.1016/j.jnutbio.2017.01.012

DO - 10.1016/j.jnutbio.2017.01.012

M3 - Article

VL - 43

SP - 11

EP - 17

JO - Nutrition Reports International

T2 - Nutrition Reports International

JF - Nutrition Reports International

SN - 1873-4847

ER -