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

Abigail Sido, Sridhar Radhakrishnan, Sung Woo Kim, Elisabeth Eriksson, Frank Shen, Qunhua Li, Vadiraja Bhat, Lavanya Reddivari, Jairam K.P. Vanamala

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)11-17
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume43
DOIs
StatePublished - May 1 2017

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Nutrition
Interleukin-6
Colon
Carcinogenesis
Diet
Inflammation
Food
Colonic Neoplasms
Interleukin-1
Swine
Edible Plants
Proteins
Anthocyanins
Cell proliferation
Biomarkers
Solanum tuberosum
Proteomics
Mass spectrometry
Mass Spectrometry
Chronic Disease

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

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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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.",
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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.

Research output: Contribution to journalArticle

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.

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