Asian Oncology Research Journal

2(1): 1-6, 2019; Article no.AORJ.52904

Beneficial Components of Colostrum for Patients: A Mini-review Focused on Oxidative Aspects and Properties of Colostrinin

Aline do Carmo França-Botelho1*

1Centro Universitário do Planalto de Araxá, Araxá, Minas Gerais, Brazil.

Author’s contribution

The sole author designed, analysed, interpreted and prepared the manuscript.

Article Information

Editor(s): (1) Dr. Bing Yan, Department of Oncology, Hainan Branch of PLA General Hospital, Haitang District of Sanya City, Hainan Province, China. Reviewers: (1) Manisha Aggarwal, Government Medical College, Patiala, India. (2) Heba Gamal Abd El-Aziz Nasr, Al-Azhar University, Egypt. (3) Flávia Del Castanhel, Federal University of Santa Catarina Florianópolis Campus, Brazil. Complete Peer review History: http://www.sdiarticle4.com/review-history/52904

Received 01 October 2019 Mini-review Article Accepted 03 December 2019 Published 09 December 2019

ABSTRACT

The beneficial effect of maternal colostrum and milk on the newborn as well as on the nursing mother is well known. However, many other potentially preventive and therapeutic aspects associated with the use of components of these secretions are still partially known and have sparked some research, including in the context of cancer. A narrative mini-review to present potential beneficial effects of colostrum components for cancer patients, especially focusing on oxidative aspects and potentialities of colostrinin.

Keywords: Cancer; colostrum; nutraceuticals; colostrinin; oxidative metabolismo.

1. INTRODUCTION and / or spread to other organs. Cancer can affect almost any part of the body and has many Cancer is a generic term for a large group of anatomic and molecular subtypes that each diseases characterized by the growth of require specific management strategies. Cancer abnormal cells beyond their usual boundaries is the second leading cause of death globally and that can then invade adjoining parts of the body is estimated to account for 9.6 million deaths in ______

*Corresponding author: E-mail: [email protected];

França-Botelho; AORJ, 2(1): 1-6, 2019; Article no.AORJ.52904

2018. Lung, prostate, colorectal, stomach and mitochondria can be partially reduced by liver cancer are the most common types of generating (ROS), such cancer in men, while breast, colorectal, lung, as superoxide anion (O2-), hydrogen peroxide cervix and thyroid cancer are the most common (H2O2) and hydroxyl radical (OH-). When failure among women [1]. the balance between ROS production and elimination failure, which is called oxidative The incidence of cancer is growing globally at a stress, occurs, damage to DNA, RNA, lipids and pace that follows the aging population due to proteins can occur. In addition to DNA increased life expectancy. It is a direct result of fragmentation, the ROS can cause malfunction of the great global transformations of recent the DNA repair system, contributing to the decades, which have changed the health development of diseases, including cancer [3]. situation of peoples through accelerated urbanization, new lifestyles, new consumption The body's antioxidant defense system has the patterns [2]. primary function of inhibiting or reducing the damage to cells caused by reactive oxygen The high prevalence and mortality of cancer species. There are a wide variety of antioxidant encourages the investigation of cellular and substances, which can be classified according to molecular mechanisms that may contribute to origin and / or location into dietary antioxidants more effective preventive and therapeutic and intra and extracellular antioxidants. The means. Considering that humans are normally mechanism of action also allows them to be exposed to various cancer-inducing agents, classified as prevention antioxidants (prevent the including those obtained through diet, possible formation of free radicals), scavengers (prevent strategies involve lifestyle and diet. the attack of free radicals on cells) and repair

There is a growing interest in research involving (favor the removal of DNA molecule damage and functional and nutraceutical foods that can the reconstitution of damaged cell positively impact people's health, especially in membranes [4]. the context of cancer prevention and treatment. Given this, the present mini- Superoxide dismutase (SOD) has been reported review becomes relevant because it proposes as an important antioxidant mechanism present to present potential beneficial effects of in eukaryotes and prokaryotes, strict aerobic and colostrum components for cancer patients, microaerophil organisms. This enzyme requires a especially focusing on oxidative aspects and metal as a cofactor for its functional activity, potentialities of colostrinin. which may be copper (Cu-SOD), manganese (Mn-SOD) or iron (Fe-SOD). This enzyme acts 2. RESEARCH METHODOLOGY by catalyzing the dismutation of the superoxide anion. Dismutation is a reaction in which two This is a review of narrative literature, with identical molecules are transformed into different theoretical and contextual information plus compounds. In the case of SOD, one superoxide interpretations of the researcher considering the ion oxidizes the other, generating O2 (normal) existing scientific production. and hydrogen peroxide (H2O2). Hydrogen peroxide may be further degraded by catalase or 3. OXIDATIVE METABOLISM AND peroxidase [5].

APOPTOSIS - + 2 O 2 + 2 H ------O 2 + H 2 O 2

When you breathe, you give all your cells the Patients with neoplasia have high concentrations oxygen they need to produce energy through a of oxidizing markers and low concentrations of process known as oxidative metabolism. In short, antioxidant substances. Regarding the severity of oxygen is reduced and glucose covalent bonds the disease, it is known that the antioxidant are broken releasing carbon dioxide, water and system behaves differently according to the energy. The main cell organelle involved is the stage of cancer. As disease progresses, lower mitochondria, where several enzymes are concentrations of enzyme antioxidant markers responsible for catalyzing the stages of this are found [6]. process. In each of these steps there is the formation of byproducts that are mostly Oberley and Buettner [7] showed differences beneficial. However, approximately 5% may be between superoxide dismutase activity of cancer toxic to the cell at high concentrations. Oxygen, cells. Decreased amounts were found in many for example, during electron transport in tumors and they produced more superoxide.

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França-Botelho; AORJ, 2(1): 1-6, 2019; Article no.AORJ.52904

Tumors possess and acquire characteristics and endoplasmic reticulum and nuclear membrane abilities to maintain their survival and [14]. development. These include the ability to maintain proliferative signaling, evade growth In the context of cancer, pro-apoptotic limbs are suppressive mechanisms, resist cell death, characterized as apoptotic performers, acting as perpetuate its replicative capacity, induce tumor suppressors while pro-survival limbs are angiogenesis, and activate invasion and regarded as inhibitors, acting as metastasis. Underlying these characteristics are oncoproteins [15]. genomic instability, inflammation, imbalance of cellular energy metabolism, and the ability to Apoptosis in clinical practice is a target for evade immune destruction, which have been the potential therapeutic use of programmed cell subject of countless studies in the last decade death or for understanding the mechanisms of [8]. resistance to radiotherapy and . Many alternatives seeking cancer treatment are Tumor growth is related to a balance resulting based on the induction of tumor cell apoptosis from the sum between proliferation and cell [16]. The elucidation of some of the molecular death. Combined measurement of cell death and mechanisms of apoptosis can generate proliferation is an important weapon in the most perspectives of modulation of these processes realistic prediction of tumor behavior. The [17]. genetically controlled mechanism of cell death is 4. COLOSTRUM AND COLOSTRININ called apoptosis, which is critical for the elimination of damaged cells. Studies have Colostrum is defined as the first products of milk shown the relevance of programmed cell death in secretion, the result of the influence of lactogenic tissue homeostasis, organogenesis and tumor hormones, such as prolactin. It begins production pathogenesis [9,10]. at the end of pregnancy and continues until about 5 to 7 days after delivery. It is a Apoptosis is a fairly rapid cell death: cell secretion that has ten times more carotene than retraction occurs which causes loss of adherence mature milk, which gives it yellowish color [18]. with extracellular matrix and neighboring cells. Cell organelles maintain their morphology, Compared to milk, it has higher viscosity and is except in some cases for mitochondria, which made up of blood serum components such as may rupture the outer membrane. The chromatin immunoglobulins and other serum proteins such is condensed and concentrated near the nuclear as albumin, α-lactalbumin, β-lactoglobulin. In membrane, which remains intact. Next, the addition to containing many essential nutrients, in membrane cell shaped extensions (" blebs ") and concentrations higher than those commonly the core to disintegrate into fragments by found in milk, it also has several other beneficial membrane enveloped core. Cell membrane components such as leukocytes, growth factors, extensions increase in number and size and hormones, cytokines and nonspecific rupture, resulting in structures containing cell antimicrobial factors [19]. content. These cell portions surrounded by the cell membrane are called apoptotic bodies. These first secretions is essential passive Apoptotic bodies are rapidly phagocyted by immunity, prebiotic compounds and growth macrophages and removed without causing an factors involved in the intestinal development inflammatory process [11]. [20]. The colostrum intake is critical to the survival and health of the mammals offspring [21]. BCL-2 protein was originally described in 1985 [12] and since then other proteins with apoptosis The colostrum provides nutrition for newborns regulating properties have been identified, improves the protection against pathogens, currently resulting in the BCL-2 family. It is promotes the development of the immune therefore a set of proteins that inhibit or promote system and ensures the growth, maturation and apoptosis, playing a crucial role in tissue repair of various tissues [22]. maintenance, programmed cell death during development and defense against pathogens Research demonstrates that bovine colostrum [13]. They present diverse subcellular can be administered to humans and other localization, some of which can be found in the mammals since there is a compatibility of cytosol, but most of them anchored in components with other bioactive species. Bovine membranes, such as the external mitochondrial, colostrum consumption has been

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França-Botelho; AORJ, 2(1): 1-6, 2019; Article no.AORJ.52904

recommended for symptom relief in patients polypeptides were found in human, bovine and with diarrhea, suffering from acquired goat colostrum. PRP is a 500 to 3000 Da immunodeficiency syndrome, drug-induced molecular weight peptide complex. It contains inflammatory colitis and acute phase responses 25% proline residues and 40% hydrophobic to surgery. In addition, several published studies amino acids. It is not species specific, and is have shown that bovine serum proteins may active both “in vivo" and "in vitro". Colostrinin™ have immunomodulatory, antimicrobial, antiviral, has immunomodulatory properties, including anticancer and antiulceraction [23,24,25]. The effects on humoral and cellular immune various components of colostrum can improve responses, regulatory activity in the induction of immune function and well-being of healthy Th1 and Th2 cytokines and has the ability to people, can be used as a dietary supplement, inhibit overproduction of reactive oxygen and and have therapeutic perspectives for patients nitric oxide species [29]. Colostrinin™ in the form with various pathological conditions, such as: of subminually administered tablets improves the immunodeficiencies, cardiovascular and clinical condition of Alzheimer's patients. The infectious diseases, wound healing and cancer. beneficial effect has been assigned to control Also, an advantage of colostrum supplements is and stress oxidative known implicated in the that they are well tolerated. Unlike milk, has a pathogenesis the Alzheimer's. It has been shown lower amount of lactose and therefore may be inibition of overproduction of reactive oxygen suitable for patients suffering from intolerance to species, and nitric oxide [30]. lactose [26]. Still in this context, the study by Douraghi-Zadeh, In 2009 Kanwar [27] summarized the et al. [31], through enstutors cytotoxicity components of milk breast that are of particular demonstrated that pretratment of human scientific interest in the past few years (Table 1). neuronal SHSY5Y cells with sheep colostrinina 5 microg / ml for 24 hours confers neuroprotection According to Menchetti, et al. [28], colostrum is against neurotoxicity induced by beta - amyloid . safe and has no contraindications, even at high The effect of colostrinin on LPS-stimulated doses, and reinforce that are few are clinically human peripheral blood mononuclear cells with relevant side effects. They emphasize their PHA (LP) or PMA as proinflammatory activators growing use in medicine and veterinary medicine has been the subject of research conducted by as an element that may play a complementary Zablocka, et al. [32], inhibition was 40-60% for role to synthetic pharmaceutical drugs in the PMA-induced hydrogen peroxide production. The prevention and treatment of various diseases. peptides also inhibited superoxide dismutase Milk proteins and peptides are well tolerated and activity and induced IL-6, IL-10 and TNF- many exhibit oral bioavailability; thus, they can alpha. Effects are then highlighted not only on complement standard therapies to increase adaptive immunity as already known but also on overall success in cancer treatments. Lactoferrin, innate immunity. colostrum and milk-specific peptide fractions are currently being developed as clinical nutrition for Colostrinin also stimulates the activity of natural cancer prevention and chemotherapy protection. killer cells (NK cells), leading to activity up to 10 times higher than normal, much higher than any PRP, subsequently known as Colostrinin™, was other known substance. Considering that NK first found in sheep colostrum as a fraction that cells along with the cytotoxic T cells are the main accompanies colostrums IgG2. Later, similar immune cells to attack cancer cells and virus-

Table 1. Components and respective actions of components of colostrum and breast milk

Component Actions Lactoferrin Antibacterial, antifungal, antiviral, antiparasite and antitumor. Casein Protective in experimental bacteremia, causing myelopoiesis. The casein hydrolysates were also protective in diabetic animals, reduced growth d and tumor and decreased symptoms of colic in babies. Proline Rich Promotion of T and NK cell activation; Polypeptide Protective in autoimmune disorders. Alpha-lactalbumin Antiviral, antitumor and anti-stress actions. Lactoperoxidase Antibacterial properties. Lysozyme Effective in treating periodontitis and preventing tooth decay.

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França-Botelho; AORJ, 2(1): 1-6, 2019; Article no.AORJ.52904

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Peer-review history: The peer review history for this paper can be accessed here: http://www.sdiarticle4.com/review-history/52904

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