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

Gibbons, Jessica A., Kanwar, Jagat R. and Kanwar, Rupinder K. 2015, Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer, BMC cancer, vol. 15, no. 425, pp. 1-16.

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Title Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer
Author(s) Gibbons, Jessica A.
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R. orcid.org/0000-0003-3728-9568
Kanwar, Rupinder K.
Journal name BMC cancer
Volume number 15
Issue number 425
Start page 1
End page 16
Total pages 16
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2015
ISSN 1471-2407
Keyword(s) Apoptosis
Bovine lactoferrin (bLf)
Breast cancer
Invasion
p53
Survivin
Science & Technology
Life Sciences & Biomedicine
Oncology
ANTIOXIDANT ENZYME-ACTIVITIES
GUT EPITHELIAL-CELLS
OXIDATIVE STRESS
SMALL-INTESTINE
IN-VIVO
FE-BLF
COLON
RAT
CARCINOGENESIS
PROTEINS
Summary BACKGROUND: Iron 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 Fe(3+) however, it has been demonstrated that manipulating the saturation state can enhance bLf's anti-cancer activities. METHODS: Apo-bLf (Fe(3+) free) and Fe-bLf (>90% Fe(3+) 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. RESULTS: Apo-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. CONCLUSIONS: The 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.
Language eng
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075689

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.