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.
Introduction:
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. [1]. Lf comprises of ,700 amino acids with two symmetrical lobes forming a single polypeptide chain. Each lobe is further subdivided into two domains that harbor the iron binding sites [2]. In its natural form, native monomeric-bLf (NM-bLf) is approximately 15-20% saturated with Fe3+ ions [3]. 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].
More recently, 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]. Because of the worldwide interest in bLf’s health and medical applications, investigators for several decades have searched for the most convenient way to produce bLf. Today, native ,78– 80 kDa bLf is mostly produced at a commercial scale from skim milk or whey and bovine colostrum (BC) [4]. When compared to milk, BC is a naturally rich source of bLf, known to contain 1.5– 5.0 g L21 of bLf. BC is a thick yellow fluid produced during the first few days after calf’s birth. It is known to contain immune, and growth factors to support the growth of the young calf, and also to prevent gastrointestinal infections until the calf develops its own active immune defense
Identification of Unprecedented Anticancer Properties of High Molecular Weight Biomacromolecular Complex Containing Bovine Lactoferrin (HMW-bLf) Fawzi Ebrahim1.”¤ , Jayanth Suryanarayanan Shankaranarayanan1.” , Jagat R. Kanwar1 , Sneha Gurudevan1 , Uma Maheswari Krishnan2 , Rupinder K. Kanwar1 * 1 Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia, 2 Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical & Biotechnology, SASTRA University, Thanjavur, India
