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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Brewers’ rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats
Bee Ling Tan, Mohd Esa Norhaizan, Ky Huynh, Swee Keong Yeap, Hamzah Hazilawati, Karim Roselina
Bee Ling Tan, Mohd Esa Norhaizan, Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Mohd Esa Norhaizan, Research Centre of Excellent, Nutrition and Non-Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Mohd Esa Norhaizan, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Ky Huynh, Swee Keong Yeap, Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Hamzah Hazilawati, Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Karim Roselina, Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Author contributions: Tan BL, Norhaizan ME, Yeap SK and Roselina K designed the study; Tan BL carried out the experiments; Tan BL and Huynh K performed acquisition of data; Tan BL, Norhaizan ME and Hazilawati H performed the statistical analysis and interpretation of data; Tan BL and Norhaizan ME drafted the manuscript and revised the manuscript critically; all authors read and approved the final version of the manuscript.
Supported by Ministry of Education, Malaysia (RUGS-2 project, No. 05-02-12-1862RU).
Institutional review board statement: This study was conducted following the guidelines approved by the Institutional Animal Care and Use Committee of the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Selangor.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Selangor (IACUC protocol number: UPM/FPSK/PADS/BR-UUH/00461).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mohd Esa Norhaizan, PhD, Associate Professor, Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
nhaizan@upm.edu.my
Telephone: +603-89472427 Fax: +603-89426769
Received: December 30, 2014
Peer-review started: January 1, 2015
First decision: March 10, 2015
Revised: April 10, 2015
Accepted: June 10, 2015
Article in press: June 10, 2015
Published online: August 7, 2015
Processing time: 221 Days and 0.5 Hours
AIM: To investigate the mechanistic action of brewers’ rice in regulating the Wnt/nuclear factor-kappa B (NF-κB)/Nrf2-signaling pathways during colon carcinogenesis in male Sprague-Dawley rats.
METHODS: Male Sprague-Dawley rats were randomly divided into the following five groups (six rats in each group): (G1) normal, (G2) azoxymethane (AOM) alone, (G3) AOM + 10% (weight (w)/weight (w)) brewers’ rice, (G4) AOM + 20% (w/w) brewers’ rice, and (G5) AOM + 40% (w/w) brewers’ rice. They were intraperitoneally administered 15 mg/kg body weight of AOM in saline once weekly over a two-week period and treated with an American Institute of Nutrition (AIN)-93G diet containing 10%, 20%, and 40% (w/w) brewers’ rice. The mRNA levels of glycogen synthase kinase 3β (GSK3β), β-catenin, key inflammation markers, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1)-dependent transcriptional activity were assessed by quantitative real-time polymerase chain reaction analyses. The colon superoxide dismutase, malondialdehyde, and nitric oxide levels were also analyzed to assess the antioxidant effect of these treatments. The results were analyzed using one-way analysis of variance (ANOVA), and a P value of < 0.05 was considered significant.
RESULTS: The overall analyses demonstrated that the dietary administration of brewers’ rice in AOM-induced rat colon carcinogenesis resulted in the transcriptional upregulation of GSK3β, inducible nitric oxide synthase (iNOS), Nrf2, and HO-1. We discovered that the dietary administration of brewers’ rice downregulated the β-catenin and NF-κB mRNA levels. A significant reduction in β-catenin expression was found in the groups administered with 20% (0.611 ± 0.034) and 40% (0.436 ± 0.045) (w/w) brewers’ rice compared with that of the group treated with AOM alone (1.000 ± 0.064) (P < 0.05). The NF-κB expression was significantly lower between the AOM-alone group (1.000 ± 0.048) and those groups fed with diets containing 10% (w/w) brewers’ rice (0.255 ± 0.022), 20% (w/w) brewers’ rice (0.450 ± 0.045), or 40% (w/w) brewers’ rice (0.541 ± 0.027) (P < 0.05). Brewers’ rice improved the antioxidant levels, indicating that brewers’ rice can enhance effective recovery from oxidative stress induced by AOM.
CONCLUSION: Our results provide evidence that brewers’ rice can suppress colon cancer via the regulation of Nrf2 expression and the inhibition of the Wnt/NF-κB signaling pathways.
Core tip: This study demonstrates that a treatment with 40% (w/w) brewers’ rice modulated the Wnt signaling pathway. Feeding 20% (w/w) brewers’ rice markedly improved the antioxidant level. These results strongly imply the potential use of brewers’ rice in future applications to combat oxidative stress and colon cancer.
