Anti-angiogenic properties of bovine lactoferrin

Numerous in vivo and in vitro studies have demonstrated the anticancer efficacy of bovine lactoferrin (bLF) against various types of cancer. The anti-tumor property of bLF may be partially attributable to its ability to inhibit cancer angiogenesis. This review summarizes current understanding of the inhibitory effects of exogenous bLF and lactoferricin, a cationic peptide derived from the N-terminal domain of bLF, on cancer angiogenesis. bLF inhibits angiogenesis via multiple mechanisms, including inhibition of vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 signaling as well as its anti-inflammatory and immunomodulatory properties. By contrast, human lactoferrin enhances angiogenesis in the presence of VEGF-A, suggesting that its anticancer property is achieved by a mechanism other than inhibition of cancer angiogenesis. Finally, we review the development of a drug delivery system for bLF to improve its stability and bioavailability. • The anti-tumor property of bLF may be partly due to its anti-angiogenic effect. • Administration of bLF downregulates angiogenesis in mice implanted with tumor cells. • bLF inhibits tube formation of vascular endothelial cells in vitro. • LFcinB inhibits angiogenesis by binding to cell surface HSPGs.