Abstract
With the successful clinical trials, multifunctional glycoprotein bovine lactoferrin is gaining attention as a safe nutraceutical and biologic drug targeting cancer, chronic-inflammatory, viral and microbial diseases. Interestingly, recent findings that human lactoferrin oligomerizes under simulated physiological conditions signify the possible role of oligomerization in the multifunctional activities of lactoferrin molecule during infections and in disease targeting signaling pathways. Here we report the purification and physicochemical characterization of high molecular weight biomacromolecular complex containing bovine lactoferrin (≥250 kDa), from bovine colostrum, a naturally enriched source of lactoferrin. It showed structural similarities to native monomeric iron free (Apo) lactoferrin (∼78–80 kDa), retained anti-bovine lactoferrin antibody specific binding and displayed potential receptor binding properties when tested for cellular internalization. It further displayed higher thermal stability and better resistance to gut enzyme digestion than native bLf monomer. High molecular weight bovine lactoferrin was functionally bioactive and inhibited significantly the cell proliferation (p<0.01) of human breast and colon carcinoma derived cells. It induced significantly higher cancer cell death (apoptosis) and cytotoxicity in a dose-dependent manner in cancer cells than the normal intestinal cells. Upon cellular internalization, it led to the up-regulation of caspase-3 expression and degradation of actin. In order to identify the cutting edge future potential of this bio-macromolecule in medicine over the monomer, its in-depth structural and functional properties need to be investigated further.
Highlights
Clinical and mechanistic research over the past few decades has indicated significant relationships between nutrition and health
Our current in vitro study using breast and colon cancer cells showed for the first time the anticancer efficacy of $250 kDa high molecular weight (HMW)-biomacromolecular complex containing bLf
HMW-bLf was purified to homogeneity from Australian bovine colostrum
Summary
Clinical and mechanistic research over the past few decades has indicated significant relationships between nutrition and health. The clinical studies with bovine milk derived cancer preventive multifunctional protein lactoferrin (bLf) are currently a promising field of research. Lactoferrin (Lf) is an iron binding ,78–80 kDa glycoprotein of the transferrin family found to be widely distributed in mammalian milk and most other exocrine secretions such as tears, nasal and bronchial mucous, saliva etc. BLf’s role in mammalian iron homeostasis, organ morphogenesis, and bridging innate and adaptive immune functions has resulted in its potential applications in the medical field, along with its wide use as a current nutraceutical and a safe food supplement [1,4,5]. Based on the success of animal feeding studies and human clinical trials, bLf has gained significant attention for its prospective use as a safer anti-cancer chemopreventive and therapeutic agent [5,6,7]
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