Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer

BMC Cancer

Research Article

Jagat R. Kanwar¹  Rupinder K. Kanwar¹  Jessica A. Gibbons¹ 

[1] Nanomedicine - Laboratory for Immunology and Molecular Biomedical Research, Molecular and Medical Research Facility, School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia;

关键词: Bovine lactoferrin (bLf);    Apoptosis;    Breast cancer;    Survivin;    p53;    Invasion;   

DOI  :  10.1186/s12885-015-1441-4

 received in 2015-02-03, accepted in 2015-05-15,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIron binding, naturally occurring protein bovine lactoferrin (bLf) has attracted attention as a safe anti-cancer agent capable of inducing apoptosis. Naturally, bLf exists partially saturated (15-20%) with Fe3+ however, it has been demonstrated that manipulating the saturation state can enhance bLf’s anti-cancer activities.MethodsApo-bLf (Fe3+ free) and Fe-bLf (>90% Fe3+ Saturated) were therefore, tested in MDA-MB-231 and MCF-7 human breast cancer cells in terms of cytotoxicity, proliferation, migration and invasion. Annexin-V Fluos staining was also employed in addition to apoptotic protein arrays and Western blotting to determine the specific mechanism of bLf-induced apoptosis with a key focus on p53 and inhibitor of apoptosis proteins (IAP), specifically survivin.ResultsApo-bLf induced significantly greater cytotoxicity and reduction in cell proliferation in both cancer cells showing a time and dose dependent effect. Importantly, no cytotoxicity was detected in normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP members and their inhibitors were significantly modulated by both forms of bLf, though differentially in each cell line. Most interestingly, both Apo-bLf and Fe-bLf completely inhibited the expression of survivin protein (key IAP), after 48 h at 30 and 40 nM in cancer cells.ConclusionsThe capacity of these forms of bLf to target survivin expression and modulation of apoptosis demonstrates an exciting potential for bLf as an anti-cancer therapeutic in the existing void of survivin inhibitors, with a lack of successful inhibitors in the clinical management of cancer.

【 授权许可】

Unknown   
© Gibbons et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.