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The Use of Human, Bovine, and Camel Milk Albumins in Anticancer Complexes with Oleic Acid

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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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Acknowledgements

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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Correspondence to Vladimir N. Uversky or Elrashdy M. Redwan.

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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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