Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan ; Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan .
Proc Jpn Acad Ser B Phys Biol Sci. 2006 Nov;82(7):208-15. doi: 10.2183/pjab.82.208. Epub 2006 Nov 18.
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.
人们越来越关注高风险癌症人群的化学预防剂。我们专注于牛乳铁蛋白（bLF），这是一种 80kDa 的铁结合糖蛋白，具有抗微生物和免疫保护作用。乳铁蛋白在初乳中含量特别丰富，也存在于眼泪、唾液和精液及子宫分泌物中。然而，关于它对癌症发生的影响知之甚少。我们已经证明 bLF 及其片段肽乳铁肽（bLFcin）对大鼠化学诱导的结肠癌发生和小鼠移植癌细胞转移具有预防作用。该机制广谱，包括小肠中半胱天冬酶-1 和白细胞介素-18 的升高、细胞毒性 T 细胞和自然杀伤（NK）细胞杀伤活性的增强、抗炎和抗血管生成作用。它还抑制致癌物激活酶肝 CYP1A2 的诱导，并诱导致癌物处理大鼠结肠上皮细胞凋亡。因此，bLF 具有抑制癌症发生的多功能潜力，是人类实际应用的良好候选物。
