Cancer prevention by bovine lactoferrin and underlying mechanisms — a review of experimental and clinical studies

Abstract

In experimental studies, bovine lactoferrin (bLF) has been found to significantly inhibit colon, esophagus, lung, and bladder carcinogenesis in rats when administered orally in the post-initiation stage. Furthermore, concomitant administration with carcinogens resulted in inhibition of colon carcinogenesis, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2), which is preferentially induced by carcinogenic heterocyclic amines. Enhancement of the activities of their phase II counterparts, such as glutathione S-transferase might have also played a critical role in post-initiation suppression in a study of tongue carcinogenesis. Anti-metastatic effects were moreover detected when bLF was given intragastrically to mice bearing highly metastatic colon carcinoma 26 cells (Co 26Lu), with apparent enhancing influence on local and systemic immunity. Marked increase in the number of cytotoxic T and NK cells in the mucosal layer of the small intestine and peripheral blood cells was thus found, this in turn enhancing the production of Interleukin 18 (IL-18) and caspase-1 in the epithelial cells of the small intestine, with possible consequent induction of interferon (IFN)-gamma positive cells. Furthermore, bLF has been found to exert anti-hepatitis C virus (HCV) activity in a preliminary clinical trial in patients with chronic active hepatitis due to this virus, a main causative factor in hepatocellular carcinoma development in Japanese. More extensive clinical trials are now underway in the National Cancer Center Hospital and other institutes to further explore the preventive potential against colon carcinogenesis.

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

“…[17][18][19][20] Interestingly, in experimental studies, lactoferrin has been shown to inhibit the growth of some solid tumors such as colon, esophagus, and lung tumors. 21,22 Interestingly, stool lactoferrin has been shown to be a sensitive marker of intestinal inflammation in patients with intestinal tract symptoms and is being used in clinical practice to identify patients with intestinal tract inflammation. 23 Our results suggest that the detection of lactoferrin protein levels in the stool might also be a practical noninvasive screening test for pancreatic inflammation or cancer invasion among patients with suspected pancreatic disease.…”

Induction of lactoferrin gene expression by innate immune stimuli in mouse mammary epithelial HC-11 cells

“…Therefore, increased recruitment of neutrophils and compliment with an increase of lactoferrin production by epithelial cells occurs in the initial phase of infection. Although there has been extensive research efforts on the structure-function relationship of LF and its application in nutritional supplement and prevention of infections and cancers [8][9][10][11][12], studies on the regulation of LF expression by physiological stimuli has been limited [13,14].…”

Liposomalization of Lactoferrin Enhanced It's Anti-inflammatory Effects via Oral Administration

“…It is considered to be a bioactive milk protein that plays versatile roles in the immune system responses and helps to protect the body from various infections. 5,6) Many studies have already demonstrated that bovine lactoferrin (bLF) features a variety of bioactivities such as anti-bacterial, [6][7][8][9] antiviral, [10][11][12] anti-oxidative, 13) anti-tumor, [14][15][16] anti-inflammatory, [17][18][19][20] immunomodulatory, 21) analgesic 22) and antistress 23) effects. Recently, it has also been reported that oral administration of bLF to patients suffering chronic hepatitis C reduced the amount of hepatitis C virus.…”