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Anticancer and Immunomodulatory Activity of Egg Proteins and Peptides: a Review

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Anticancer and Immunomodulatory Activity of Egg Proteins and Peptides: a Review Anticancer and immunomodulatory activity of egg proteins and peptides: a review J. H. Lee and H.-D. Paik1 Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Korea ABSTRACT Eggs are widely recognized as a highly mortality worldwide, and therefore research aimed at nutritious food source that offer specific health benefits developing new treatments for cancer immunotherapy for humans. Eggs contain all of the proteins, lipids, vi- is of great interest. The present review focuses primar- tamins, minerals, and growth factors necessary for em- ily on the anticancer and immunomodulatory activities bryonic development. In particular, egg white and yolk of egg proteins and their peptides and provides some proteins are considered functional food substances be- insight into their underlying mechanisms of action. A cause they possess biological activities such as antimi- number of egg proteins and peptides have been reported crobial, antioxidant, metal-chelating, antihypertensive, to induce apoptosis in cancer cells, protect against anticancer, and immunomodulatory activities. Peptides DNA damage, decrease the invasion ability of cancer produced via processes such as enzymatic hydroly- cells, and exhibit cytotoxic and antimutagenic activity sis, fermentation by microorganisms, and some chemi- in various cancer cell lines. Furthermore, egg proteins cal and physical treatments of egg proteins have been and peptides can stimulate or suppress pro- or anti- shown to enhance the functional properties and solu- inflammatory cytokines, as well as affect the production bility of these peptides. Peptide activity is strongly re- of inflammatory mediators in a variety of cell lines. In lated to amino acid sequence, composition, and length. addition, the composition of eggs and the processes of At present, cancer remains among the leading causes of egg proteins and peptides production will be discussed. Key words: egg protein, egg peptide, functional activity, anticancer activity, immunomodulatory activity 2019 Poultry Science 98:6505–6516 http://dx.doi.org/10.3382/ps/pez381 INTRODUCTION fore, bioactive materials that display anticancer and immunomodulatory activity are beginning to be stud- Eggs are a highly nutritious food source that offer ied. Ginseng is the most popular natural material in specific health benefits to humans. It is well known that this field, and many reports have described its im- eggs contain all of the nutrients necessary to maintain munomodulatory activity (Hwang et al., 2019;Kang a developing embryo, including proteins, lipids, vita- et al., 2019; Liu et al., 2019; Vinh et al., 2019; Yi, mins, minerals, and growth factors. In addition, eggs 2019). In addition to this, extracts from various plants are an excellent source of protein of high biological value (Ahmad et al., 2018; Alaklabi et al., 2018;Dong (Froning, 2006). A number of studies have shown that et al., 2018; Wang et al., 2018; Ma et al., 2019), com- egg proteins possess many important biological activ- pounds from marine products (Murugan and Iyer, 2014; ities including antioxidant, antimicrobial, and antihy- Fernando et al., 2018; Yang et al., 2019b) and some pro- pertensive properties. biotics (Haghshenas et al., 2015; Yang et al., 2019a; Today, the prevention and treatment of cancer as well Zhao et al., 2019) are reported to have anticancer as immunomodulation and immune stimulation are of or immunomodulatory activities. In particular, pro- great interest to the food and pharmaceutical indus- teins and peptides obtained from various sources— tries. Cancer, characterized by uncontrolled cell pro- including soy (Kim et al., 2000; Kong et al., 2008), liferation and metastasis to many parts of the body, whey (Mercier et al., 2004; Saint-Sauveur et al., 2008; remains one of the leading causes of mortality world- Attaallah et al., 2012), plant seed (Udenigwe et al., wide, and cancer immunotherapy is an important as- 2009; Liu et al., 2018), and fish proteins (Hsu et al., pect of cancer research and treatment (El-Gohary and 2011; Hou et al., 2012; Halldorsdottir et al., 2014;Kim Shaaban, 2017; Lohmueller and Finn, 2017). There- et al., 2018)—have been found to have anticancer and immunomodulatory activities. Egg white and egg yolk are rich in proteins such C 2019 Poultry Science Association Inc. as ovalbumin, ovotransferrin, ovomucin, ovomucoid, Received September 3, 2018. Accepted June 11, 2019. lysozyme, IgY, and phosvitin. Many studies have been 1Corresponding author: [email protected] undertaken to identify novel functional activities of egg 6505 6506 LEE AND PAIK proteins and to produce functional peptides from these composed of mannose and glucosamine (Sugino et al., proteins. In this review, the composition of eggs and 1996). the processes used to produce egg proteins and pep- tides have been discussed. Furthermore, their functional activities have been reviewed, with a specific focus on anticancer and immunomodulatory properties. METHODS FOR SEPARATION OF EGG PROTEINS AND PREPARATION OF CHEMICAL COMPOSITION OF THE EGG PEPTIDES Egg Shell Various methods have been used to separate and pu- rify proteins from egg white and egg yolk. Initially, Egg shell is composed of minerals, proteins, and wa- salts such as ammonium sulfate, sodium chloride, or ter. Minerals are the major component (approximately potassium chloride were used to separate ovalbumin 91%) and include compounds of calcium (98%), mag- (Warner and Weber, 1951), ovotransferrin (Fraenkel- nesium (0.9%), and phosphorus (0.9%) (Sugino et al., Conrat and Feeney, 1950), ovomucin (Brooks and Hale, 1996). Egg shell consists of an outer layer (the cuticle) 1959), and phosvitin (Mecham and Olcott, 1949). How- and an inner layer (the shell membrane). The cuticle ever, the purity of these isolated proteins was very layer is composed of proteins and a small amount of low. Chromatography methods are now commonly used carbohydrates and lipids, and the shell membrane con- to separate egg proteins. Ovalbumin (Sakakibara and tains a small amount of protoporphyrin. Yanagisawa, 2007), lysozyme (Li-Chan et al., 1986), ovotransferrin (Croguennec et al., 2001), and phosvitin (Lei and Wu, 2012) were separated by ion ex- Egg White change chromatography. Ovotransferrin (Al-Mashikhi and Nakai, 1987), IgY (Jiang et al., 2016), and lysozyme Egg white accounts for approximately 60% of the to- (Junowicz and Charm, 1975) can be separated by affin- tal weight of the egg. Water and proteins are the ma- ity chromatography. These chromatographic methods jor components of egg white, accounting for roughly can yield high-purity proteins. Nonetheless, they are 88 and 10.4%, respectively (Sugino et al., 1996). Car- not suitable for large-scale production because of the bohydrates, lipids, and minerals are minor constituents high cost, the slowness of the process, and the low ca- (less than 1%). Egg white consists of various proteins, of pacity. Ultrafiltration is a suitable method for the sep- which ovalbumin is the most abundant (54%), followed aration and purification of egg proteins. Many egg pro- by ovotransferrin (12%), ovomucoid (11%), ovoglob- teins such as ovalbumin (Datta et al., 2009), lysozyme ulin (4%), ovomucin (3.5%), lysozyme (3.4%), ovo- (Wan et al., 2006), and IgY (Hernandez-Campos et al., macroglobulin (0.5%), and other, less abundant pro- 2010) can be separated by ultrafiltration. However, teins. Egg white contains a trace amount of lipids these ultrafiltration methods are highly complex and (0.02%) (Sato et al., 1973) and includes minerals, such are strongly affected by operating and physicochemical as compounds of sulfur, potassium, sodium, chlorine, conditions; therefore, despite the fact that they yield phosphorus, calcium, magnesium, and iron. Carbohy- purity values greater than 90%, they cannot be scaled drates exist in egg white in both a free (0.4% of egg up. white) and bound (0.5% of egg white) form. Glucose Many peptides produced from egg proteins offer not accounts for the majority of free carbohydrates (98%) only nutritional value but also bioactivities. These pep- in egg white (Sugino et al., 1996). tides often have no bioactivity in the native protein and must undergo proteolysis to acquire their specific Egg Yolk bioactivities (Korhonen and Philanto, 2006). The most popular method for the production of functional pep- Egg yolk constitutes approximately 28% of the whole tides is enzymatic hydrolysis by means of commercial egg by weight, and the main component is lipids (60% enzymes. Protease, trypsin, pepsin, α-chymotrypsin, by dry weight) (Sugino et al., 1996). Egg yolk lipids alcalase, and papain are used for proteolysis (Mine largely consist of triglycerides, phospholipids, choles- et al., 2004; Pellegrini et al., 2004; Moon et al., 2013; terol, and cerebroside. Most egg yolk proteins are in the Abeyrathne et al., 2016). These commercial enzymes form of low-density lipoprotein (LDL) and high-density are effective at producing peptides because their spe- lipoprotein (HDL). LDL accounts for 65% of total egg cific features, such as optimal pH, optimal tempera- yolk protein and is responsible for its emulsifying prop- ture, and cleavage site, are well known. Additionally, erties. Phosvitin, livetin, and riboflavin-binding pro- some physical methods such as high pressure and heat teins are also present in egg yolk. The latter contains 1% treatments are employed for enzymatic hydrolysis to in- minerals, the most abundant of which is phosphorus. crease enzymatic
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