Abstract
Homeostasis in the human body results from the tight regulation of several events, since too little inflammation disrupts the process of tissue repair and remodeling, whereas too much exerts a collateral effect by causing tissue damage with life-threatening consequences. In some clinical conditions, such as inflammatory bowel disease (IBD), inflammation functions as a double-edged sword by either enabling or inhibiting cancer development and progression. Generally, cancer develops through evasion mechanisms that regulate cell growth, causing a high rate of uncontrolled proliferation, and mechanisms for evading cell death, such as apoptosis. Moreover, chronic inflammation is a factor that contributes to colorectal cancer (CRC), as observed in individuals with IBD; all these conditions favor an increased rate of angiogenesis and eventual metastasis. Lactoferrin (Lf) is a mammalian iron-binding multifunctional glycoprotein regarded as a natural compound that up- and downregulates both humoral and cellular components of immunity involved in regulating the inflammatory response and maintaining gut homeostasis. Human and bovine Lf share high sequence homology and have very similar antimicrobial, anti-inflammatory, and immunomodulatory activities. Bovine Lf from milk is considered a safe molecule and is commercially available in large quantities. This review mainly focuses on the regulatory effects of orally administered bovine Lf on the inflammatory response associated with CRC; this approach indicates that CRC is one of the most frequently diagnosed cancers and affects the intestinal tract with high clinical and epidemiologic relevance. Thus, this review may provide foundations for the potential use of bovine Lf alone or as a natural adjunct agent to increase the effectiveness and reduce the side effects of anticancer chemotherapy.
Highlights
The aim of this review is mainly to discuss the effects of bovine Lf on colorectal cancer (CRC) and the inflammatory response associated with this disease
CRC has a genetic background in individuals with familial adenomatous polyposis and hereditary nonpolyposis, whereas in patients with inflammatory bowel disease (IBD), cancer is associated with chronic inflammation (Itzkowitz and Yio, 2004)
Chronic inflammation may cause the loss of cellular homeostasis and trigger cellular alterations, including carcinogenesis
Summary
The aim of this review is mainly to discuss the effects of bovine Lf (bLf) on colorectal cancer (CRC) and the inflammatory response associated with this disease. Some diseases are associated with a high risk of CRC, such as familial adenomatous polyposis and hereditary nonpolyposis CRC, as well as clinical variants of inflammatory bowel diseases (IBDs), mainly ulcerative colitis and Crohn’s disease (Itzkowitz and Yio, 2004; Cutone et al, 2020). In CRC associated with colitis, several forms of epithelium dysplasia are observed: polypoid or flat, localized, diffuse or multifocal (Itzkowitz and Yio, 2004). Several factors, such as the interaction with the gut microbiota, genetic background, and immune framework, provide conditions for tumor development that are more frequently found in the colon than in the small intestine (Pancione et al, 2014)
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