Abstract
Oleic acid (OA) is a monounsaturated fatty acid that upon binding to milk proteins, such as α-lactalbumin and lactoferrin, forms potent complexes, which exert selective anti-tumor activity against malignant cells but are nontoxic for healthy normal cells. We showed that the interaction of OA with albumins isolated from human, bovine, and camel milk results in the formation of complexes with high antitumor activity against Caco-2, HepG-2, PC-3, and MCF-7 tumor cells. The antitumor effect of the complexes is mostly due to the action of oleic acid, similar to the case of OA complexes with other proteins. Viability of tumor cells is inhibited by the albumin-OA complexes in a dose dependent manner, as evaluated by the MTT assay. Strong induction of apoptosis in tumor cells after their treatment with the complexes was monitored by flow cytometry, cell cycle analysis, nuclear staining, and DNA fragmentation methods. The complex of camel albumin with OA displayed the most pronounced anti-tumor effects in comparison with the complexes of OA with human and bovine albumins. Therefore, these results suggest that albumins have the potential to be used as efficient and low cost means of tumor treatment.
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Abbreviations
- α-LA:
-
α-Lactalbumin
- BAMLET:
-
Bovine α-LA made lethal to tumor cells
- BSA:
-
Bovine albumin
- BSA-OA:
-
Complex of bovine albumin with oleic acid
- Caco-2:
-
Human colon cancer cells
- CAMLET:
-
Camel α-LA made lethal to tumor cells
- CSA:
-
Camel albumin
- CSA-OA:
-
Complex of camel albumin with oleic acid
- DMEM:
-
Dulbecco’s modified eagle’s medium
- DMSO:
-
Dimethyl sulfoxide
- EPR:
-
Enhanced permeation retention
- FBS:
-
Fetal bovine serum
- GAMLET:
-
Goat α-LA made lethal to tumor cells
- HAMLET:
-
Human α-LA made lethal to tumor cells
- HepG2:
-
Human hepatoma cells
- HDF:
-
Human dermal fibroblast cells
- HSA:
-
Human albumin
- HSA-OA:
-
Complex of human albumin with oleic acid
- MCF-7:
-
Human breast tumor cells
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide
- OA:
-
Oleic acid
- PC-3:
-
Prostate cancer cells
- PI:
-
Propidium iodide
- RPMI:
-
Roswell Park Memorial Institute
- SA:
-
Serum albumin
- SAXS:
-
Small angle X-ray scattering
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This work was partially supported by the Russian Foundation for Basic Research (Grant No. 16-34-60229 to E.A.L.).
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El-Fakharany, E.M., Abu-Serie, M.M., Litus, E.A. et al. The Use of Human, Bovine, and Camel Milk Albumins in Anticancer Complexes with Oleic Acid. Protein J 37, 203–215 (2018). https://doi.org/10.1007/s10930-018-9770-1
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DOI: https://doi.org/10.1007/s10930-018-9770-1