Liposomalization of lactoferrin enhanced its anti-tumoral effects on melanoma cells

Abstract

A number of studies have reported the anti-tumoral activity of lactoferrin, a property mediated by a variety of mechanisms such as inhibitory effects on tumor cell growth, NK cell activation, and enhancement of apoptosis. Liposomes are known to be an efficient drug delivery system which can enhance the therapeutic potential of the encapsulated compounds. We have used positively charged liposomes composed of phosphatidylcholine (PC), dioleoylphosphatidylethanolamine (DOPE), cholesterol (Chol) and stearylamine (SA) (6:1:2:1 M ratio) as a carrier system for bovine iron-free Lf (ApoBLf), and compared the in vitro effect of free and liposome-entrapped ApoBLf on the growth and morphology of murine melanoma B16-F10 cells. Liposomal formulation of ApoBLf was found to enhance the capacity of the protein to inhibit the cell proliferation by affecting cell cycle progression. The effect appeared to be due to the capacity of liposomes to increase the uptake of the protein and its accumulation into cells and probably to protect it from degradation, as revealed by fluorescence microscopy and flow cytometry. Our results demonstrate the ability of liposomes to improve the anti-tumor activity of Lf and suggest that liposomal protein may have a potential therapeutic use in the prevention and/or treatment of cancer diseases.

Identification of Unprecedented Anticancer Properties of High Molecular Weight Biomacromolecular Complex Containing Bovine Lactoferrin (HMW-bLf)

“…Similarly, another study has shown that the anti-tumor effects of NM-bLf on melanoma cells can be enhanced with liposomalization. A lipid delivery system (liposomes) was used to prevent the NM-bLf from proteolysis or neutralization by serum proteins [35]. Considering the findings that tetramer is reported to be the dominating form of hLf observed under physiological conditions [10], [23], and bLf self-associates as dimers, trimers and tetramers in mammary secretions during infection and involution [12], [19], it may imply that the physiological existence of Lf oligomers, can therefore be a protection strategy acquired by multifunctional Lf against proteolysis or neutralization by serum proteins.…”

Camel Milk Triggers Apoptotic Signaling Pathways in Human Hepatoma HepG2 and Breast Cancer MCF7 Cell Lines through Transcriptional Mechanism

“…Among these mediators, lactoferrin, an iron-binding glycoprotein, is known to exert in vitro and in vivo antitumor activity [36]. In this context, it has been recently reported that lactoferrin inhibits the development of cancer through inhibiting CYP1A1 activation in 7,12-dimethylbenz[a]anthracene (DMBA-) induced hamster buccal pouch carcinoma model.…”

Camel Milk Modulates the Expression of Aryl Hydrocarbon Receptor-Regulated Genes,Cyp1a1, Nqo1, andGsta1, in Murine hepatoma Hepa 1c1c7 Cells

“…In addition, ongoing research in our laboratory has shown the presence of several compounds in camel milk that could be involved in milk-mediated effect (unpublished data). Among these mediators, lactoferrin, an iron-binding glycoprotein, is known to exert in vitro and in vivo antitumor activity [37]. In this context, it has been recently reported that lactoferrin inhibits the development of cancer through inhibiting CYP1A1 activation in 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hamster buccal pouch carcinoma model.…”