Journal List > J Nutr Health > v.51(1) > 1081549

J Nutr Health. 2018 Feb;51(1):14-22. Korean.
Published online February 28, 2018.  https://doi.org/10.4163/jnh.2018.51.1.14
© 2018 The Korean Nutrition Society
Effects of luteolin on chemical induced colon carcinogenesis in high fat diet-fed obese mouse
Jeong-Eun Park and Eunjung Kim
Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan 38430, Korea.

To whom correspondence should be addressed. tel: +82-53-850-3523, Email: kimeunj@cu.ac.kr
Received February 02, 2018; Revised February 18, 2018; Accepted February 19, 2018.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Purpose

Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice.

Methods

Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days.

Results

Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma TNF-α and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT.

Conclusion

Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.

Keywords: colon cancer; high fat diet; obesity; mouse; luteolin

Figures


Fig. 1
Weight and length of large intestine. The entire large intestine from cecum to rectum was taken out and the length of large intestine was measured with a ruler. The large intestine was weighed after flushing out luminal contents with phosphate buffered saline. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 by Duncan's multiple range test. The alphabet a in the figure was given to the largest number. ND, normal diet; HFD, high fat diet; HFD LL, HFD + 0.0025% luteolin; HFD HL, HFD + 0.005% luteolin
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Fig. 2
Chemopreventive effect of luteolin in high fat diet-fed C57BL/6 mouse. After colon carcinogenesis experiment, the entire large intestine was taken out, open longitudinally and the number of tumors was counted macroscopically. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 by Duncan's multiple range test. The alphabet a in the figure was given to the largest number. ND, normal diet; HFD, high fat diet; HFD LL, HFD + 0.0025% luteolin; HFD HL, HFD + 0.005% luteolin
Click for larger image


Fig. 3
Anti-inflammatory effects of luteolin in high fat diet-fed C57BL/6 mouse. (A) Plasma TNF-α was measured as described in the methods. (B) The distal part of large intestine was immunoblotted with relevant antibodies. Photograph of chemiluminescent detection of the representative blots (left). The relative abundance of each band to its own β-actin was quantified (right). (C) Rectum was removed and fixed in 10% formalin. Tissue sections were stained with antibody against iNOS and photographed at × 200. (a) ND (b) HFD (c) HFD LL (d) HFD HL. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 by Duncan's multiple range test. The alphabet a in the figure was given to the largest number. ND, normal diet; HFD, high fat diet; HFD LL, HFD + 0.0025% luteolin; HFD HL, HFD + 0.005% luteolin
Click for larger image

Tables


Table 1
Composition of experimental diets
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Table 2
Daily food intake and body weight change
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Notes

This work was supported by research grants from Daegu Catholic University in 2012.

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