Lactoferrin enhances Fas expression and apoptosis in the colon mucosa of azoxymethane-treated rats

Abstract

Bovine lactoferrin, a multifunctional glycoprotein, has been shown to strongly inhibit development of azoxymethane (AOM)-induced rat colon tumors. Little, however, is known about the inhibitory mechanisms. We have demonstrated recently that lactoferrin enhances the expression of a member of the tumor necrosis factor receptor family, Fas, in the colon mucosa during both early and late stages of carcinogenesis. Thus, Fas could be involved in bovine lactoferrin-mediated inhibition of tumor development. To investigate this possibility, we studied the influence of bovine lactoferrin on Fas-mediated apoptosis with regard to expression of Fas, activation of caspase-8 and caspase-3, and DNA fragmentation in the colon mucosa of AOM-treated rats. Western blot analysis demonstrated a >2.5-fold increase in Fas protein expression, as well as elevation of the active forms of both caspase-8 and caspase-3. Immunohistochemical analysis revealed Fas-positive cells and apoptotic cells preferentially within the proximal colon region, clearly at the site of bovine lactoferrin-mediated tumor inhibition. These results suggest that apoptosis caused by elevated expression of Fas is involved in chemoprevention by lactoferrin of colon carcinogenesis.

Pepsin-Digested Bovine Lactoferrin Induces Apoptotic Cell Death With JNK/SAPK Activation in Oral Cancer Cells

“…This suggests that Lfc B is present in the Lfn-p fraction and is also implicated as an apoptotic stimulus in SAS cells. Recently, the role of activation of caspase-3, one of the most common mediators of apoptosis, in Lfn-induced apoptotic change was studied in the colon mucosa of azoxymethane-treated rats (10). The authors also reported that caspase-3 activation was the result of induction of Fas, a member of tumor necrosis factor (TNF) receptor family, and activation of caspase-8, an initiator caspase for caspase-3.…”

“…Bovine Lfc induces apoptotic cell death by producing reactive oxygen species (ROS) in human leukemia cell lines in vitro (8). Recently, it was found that Lfn changed apoptosis-related gene expression in colon mucosa (10) and a head/ neck cancer cell line (11). However, the exact mechanism underlying cell death induced by Lfn and Lfc remains unclear.…”

Lactoferrin: a review

“…Nevertheless, the exact mechanism of this function has not been discovered so far (Fujita et al, 2004).…”

Therapeutic Applications of Camel’s Milk and Urine against Cancer: Current Development Efforts and Future Perspectives

“…Lactoferrin inhibit the proliferation of cancer cells by various mechanisms. One of such mechanism includes that it interacts with polysaccharides ligands on cell surfaces and activate cell signaling pathways such as the Fas pathway thereby inhibit the growth of tumor by apoptosis [93]. Lactoferrin can also penetrate cells and function as a transcription factor and activating the transcription of specific DNA sequences [38,94].…”