Evidence for a direct antitumor mechanism of action of bovine lactoferricin.

Background: Bovine lactoferrin (LFB) and its pepsin-generated peptide lactoferricin (LfcinB) possess antitumor activities. The mechanism underlying the antitumor activities of LfcinB in vivo has not been elucidated. In this study the antitumor activities exerted by LFB, LfcinB and murine lactoferricin (LfcinM) on murine tumor cell lines and experimental tumors were investigated. Materials and Methods: The protein and peptides were tested against Meth A fibrosarcoma, B16F10 melanoma and C26 colon carcinoma cells in vitro and their derived tumors in vivo, exploring the mechanisms of antitumor activity by way of histological and scanning electron microscopical studies. Results: LfcinB exerted significant cytotoxic activity against the three tumor cell lines in vitro and significantly reduced the size of solid Meth A tumors. Scanning electron micrographs revealed tumor cell membrane disruption and eventually cell lysis, while extensive hemorrhagic necrosis was apparent in tumor sections one day after LfcinB treatment. No species-specific antitumor effect of LfcinM was observed. Conclusion: Our study demonstrated that LfcinB elicits an antitumor effect mediated through a direct mechanism of action not observed with LFB or LfcinM.