Immunomodulatory lactoferrin in the regulation of apoptosis modulatory proteins in cancer

Lactoferrin (Lf), an iron binding ~80 kDa glycoprotein is a well characterized multifunctional protein found to be present in mammalian milk and in most exocrine secretions. Besides Lf’s important physiological roles in the process of iron homeostasis, iron transportation and sequestration, it is well known for its properties such as anti-microbial, antiviral anti-inflammatory and immunomodulatory functions. In the recent decade, Lf has gained significant attention for its future potential use as a safer natural food (bovine milk) derived anti-cancer therapeutic. With regards to Lf’s chemopreventive effects in targeting carcinogenesis, both animal and human studies have widely reported its immunomodulatory properties to play a significant role. The deregulation of apoptosis (programmed cell death) mechanisms has not only major implications for the development of uncontrolled tumour growth but evasion of apoptosis is also an important factor affecting drug resistance and radioresistance in cancer. With the exception of few studies, the molecular basis by Lf treatment remains unclear. In this review, by addressing the main features of Lf’s structure and function we discuss the recent developments in delineating the therapeutic mechanisms of Lf and its effects on the proteins and receptors modulating apoptosis.