Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer
| Autor: | Rupinder K. Kanwar, Jagat R. Kanwar, Jessica Gibbons |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
p53
Cancer Research medicine.medical_specialty Cell Survival Survivin Antineoplastic Agents Breast Neoplasms Apoptosis medicine.disease_cause Inhibitor of Apoptosis Proteins Breast cancer Invasion Cell Movement Cell Line Tumor Internal medicine Genetics medicine Animals Humans Annexin A5 Lactate Dehydrogenases Caspase Cell Proliferation Dose-Response Relationship Drug biology business.industry Lactoferrin Cell growth Correction Epithelial Cells Endocrinology Oncology Caspases MCF-7 Cells biology.protein Cancer research Cattle Female Bovine lactoferrin (bLf) business Carcinogenesis Oxidative stress Research Article |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-015-1441-4 |
| Popis: | 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 Fe3+ however, it has been demonstrated that manipulating the saturation state can enhance bLf’s anti-cancer activities. Methods Apo-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. 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. |
| Databáze: | OpenAIRE |
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