International Journal of Molecular Sciences Review Hypotheses on the Potential of Rice Bran Intake to Prevent Gastrointestinal Cancer through the Modulation of Oxidative Stress Bernard M. H. Law, Mary M. Y. Waye, Winnie K. W. So and Sek Ying Chair * The Nethersole School of Nursing, The Chinese University of Hong Kong, Shatin, The New Territories, Hong Kong, China; [email protected] (B.M.H.L.); [email protected] (M.M.Y.W.); [email protected] (W.K.W.S.) * Correspondence: [email protected]; Tel.: +852-3943-6225 Received: 23 May 2017; Accepted: 20 June 2017; Published: 24 June 2017 Abstract: Previous studies have suggested the potential involvement of oxidative stress in gastrointestinal cancers. In light of this, research efforts have been focused on the potential of dietary antioxidant intake to prevent gastrointestinal cancer through the modulation of oxidative stress. Rice bran, a by-product of rice milling, has been shown to contain an abundance of phytochemicals, which are dietary antioxidants. To date, a number of studies have shown the antioxidative effect of rice bran intake, and some demonstrated that such an effect may contribute to gastrointestinal cancer prevention, largely through the antioxidative properties of rice bran phytochemicals. In addition, these phytochemicals were shown to provide protection against cancer through mechanisms linked to oxidative stress, including β-catenin-mediated cell proliferation and inflammation. The present article provides an overview of current evidence for the antioxidative properties of rice bran and its phytochemicals, and for the potential of such properties in cancer prevention through the oxidative-stress-linked mechanisms mentioned above. The article also highlights the need for an evaluation of the effectiveness of rice bran dietary interventions among cancer survivors in ameliorating oxidative stress and reducing the level of gastrointestinal cancer biomarkers, thereby establishing the potential of such interventions among these individuals in the prevention of cancer recurrence. Keywords: rice bran; oxidative stress; gastrointestinal cancer; cancer prevention; antioxidants 1. Introduction Gastrointestinal cancers, defined as those occurring at various sites that include the colon, rectum, stomach, liver, pancreas and oesophagus, form one of the most common cancer groups worldwide. In 2012, more than 3.8 million new cases of gastrointestinal cancer were reported worldwide, and its incidence is expected to increase to almost 6.2 million by 2030 [1]. Therefore, there is a pressing need for the development of effective strategies to prevent gastrointestinal cancers. Previous research has focused on seeking a better understanding of the molecular mechanisms of gastrointestinal carcinogenesis. During the years of research, a number of physiological factors have been identified concerning such mechanisms. For example, it was suggested that colorectal cancer (CRC) can be caused by intestinal inflammation and microbial dysbiosis [2], while stomach cancer was found to be the result of Helicobacter Pylori infections [3,4]. However, among all the various cancer-associated physiological factors, oxidative stress appears to be one of the most studied to date. In the light of this, research has been directed towards the potential use of dietary antioxidants, the edible compounds known to reduce oxidative stress, in cancer chemoprevention. Likewise, previous research has also focused on whether the intake of certain foods generally consumed by Int. J. Mol. Sci. 2017, 18, 1352; doi:10.3390/ijms18071352 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2017, 18, 1352 2 of 20 humans conferred a protective effect against oxidative stress. Rice bran, a by-product of rice milling previously shown to contain a variety of bioactive compounds that exhibit antioxidant properties, is one of the food sources that have been widely studied for their antioxidant and anticancer potential. The aim of the present paper is to provide an overview of current data on the anti-oxidative effect Int. J. Mol. Sci. 2017, 18, x 2 of 20 of rice bran, and the potential mechanisms of how such effect may lead to gastrointestinal cancer prevention.previously The shown review to willcontain first a variety provide of bioactive a brief compounds account of that how exhibit oxidative antioxidant stress properties, occurs, is and the one of the food sources that have been widely studied for their antioxidant and anticancer potential. evidence supporting the hypothesis that ameliorating oxidative stress can reduce cancer risks. Studies The aim of the present paper is to provide an overview of current data on the anti-oxidative effect of that showrice thebran, antioxidative and the potential effect mechanisms of rice bran of how intake, such together effect may with lead those to gastrointestinal suggesting thatcancer rice bran intake mayprevention. prevent The cancer review through will first the provide modulation a brief account of oxidative of how stress, oxidative will stress then occurs, be reviewed. and the Finally, the potentialevidence mechanisms supporting the involved hypothesis in this that chemo-preventive ameliorating oxidative effect stress will can be reduce discussed cancer in risks. the context of findingsStudies concerning that show the the antioxidative protective effect function of rice against bran intake, oxidative together stress with those of the suggesting bioactive that compounds rice presentbran in rice intake bran. may prevent cancer through the modulation of oxidative stress, will then be reviewed. Finally, the potential mechanisms involved in this chemo-preventive effect will be discussed in the 2. Oxidativecontext Stress of findings concerning the protective function against oxidative stress of the bioactive compounds present in rice bran. Oxidative stress is a condition where the rate of production of free radicals far exceeds that of their2. removal Oxidative by Stress antioxidant enzymes, therefore causing an accumulation of the former. These free radicals,Oxidative generally stress termed is a condition reactive where oxygen the rate species of production (ROS) andof free reactive radicals nitrogenfar exceeds species that of (RNS), are producedtheir removal through by antioxidant various metabolic enzymes, therefore processes, causing including an accumulation cellular of respiration the former. [These5] and free immune radicals, generally termed reactive oxygen species (ROS) and reactive nitrogen species (RNS), are reactions by immune cells [6]. While the presence of low levels of these free radicals is beneficial to produced through various metabolic processes, including cellular respiration [5] and immune cellularreactions functions by such immune as the cells regulation [6]. While ofthesignalling presence of pathways low levels of [7 ],these they free in radicals fact have is beneficial deleterious to effects on cellscellular when functions they are such produced as the regulation at high levels. of signal Indeed,ling pathways ROSand [7], they RNS in have fact have been deleterious shown to cause oxidationeffects and/or on cells nitration when they of lipids,are produced proteins at high and levels. DNA, Indeed, resulting ROS inand damage RNS have to been these shown biomolecules. to For example,cause oxidation hydroxyl and/or radical, nitration the product of lipids, of aproteins reaction and between DNA, ROSresulting such in as damage superoxide to these anion and biomolecules. For example, hydroxyl radical, the product of a reaction between ROS such as hydrogen peroxide (H2O2), can cause lipid peroxidation, protein carbonylation and the formation of superoxide anion and hydrogen peroxide (H2O2), can cause lipid peroxidation, protein carbonylation DNA adducts such as 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), all of which are markers of and the formation of DNA adducts such as 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), all of oxidativewhich stress are [ 8markers]. An RNS of oxidative such as stress peroxynitrite, [8]. An RNS formed such as by peroxynitrite, the reaction formed between by the superoxide reaction anion and nitricbetween oxide, superoxide has also beenanion shown and nitric to cause oxide, damage has also to been these shown biomolecules to cause damage [9]. A summary to these of the detrimentalbiomolecules effects of[9]. these A summary free radicals of the detrimental is provided effects in Figureof these1 free. radicals is provided in Figure 1. Figure 1.FigureA schematic 1. A schematic diagram diagram summarising summarisingthe the detrimentaldetrimental effects effects of free offree radicals radicals on biomolecules. on biomolecules. To counter the damaging effects of these free radicals, cells utilise a repertoire of antioxidant Toenzymes counter and the molecules damaging to remove effects such of these excess free free radicals,radicals and cells maintain utilise a ahealthy repertoire redox ofbalance. antioxidant enzymesFor and example, molecules superoxide to remove dismutase such (SOD) excess can scavenge free radicals superoxide and anion maintain and convert a healthy it to hydrogen redox balance. For example, superoxide dismutase (SOD) can scavenge superoxide anion and convert it to hydrogen Int. J. Mol. Sci. 2017, 18, 1352 3 of 20 peroxide, which, by the action of catalase or glutathione peroxidase (GPx), would be further detoxified. These enzymes would therefore be able to prevent the formation of the damaging ROS and RNS mentioned above.