Prevention of carcinogenesis and cancer metastasis by bovine lactoferrin

Abstract

Increasing attention is being paid to chemopreventive agents for individuals at high risk of cancer. We have concentrated on bovine lactoferrin (bLF), an 80 kDa iron-binding glycoprotein known to have anti-microbial and immunoprotective effects. Lactoferrin is particularly abundant in colostrum, and is also present in tears, saliva and seminal and uterine secretions. However, only little is known regarding its influence on carcinogenesis. We have shown preventive effects of bLF and its fragment peptide, lactoferricin (bLFcin), consisting of a 25 amino acid sequence without iron binding capacity, on chemically-induced colon carcinogenesis in the rat and transplanted carcinoma cell metastasis in the mouse. The mechanisms are wide-spectrum, including elevation of caspase-1 and IL-18 in the small intestine, enhancement of the cell killing activity of cytotoxic T and natural killer (NK) cells, and anti-inflammatory and anti-angiogenic effects. It also inhibits the induction of liver CYP1A2, a carcinogen activating enzyme, and induces apoptosis in the colon epithelium of carcinogen treated rats. Thus, bLF possesses multi-functional potential to suppress carcinogenesis and is a good candidate for practical application in humans.