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The Formation of an Anti-Cancer Complex Under Simulated Gastric Conditions

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Food Digestion

Abstract

A potent anti-cancer complex has previously been formed from two major components of milk. Human/bovine α-lactalbumin made lethal to tumour cells (H/BAMLET) is a protein–fatty acid complex that has been produced using the whey protein α-lactalbumin (α-LA) and the fatty acid oleic acid (OA). It was shown that it possesses selective anti-tumour and anti-microbial activity, which was first identified in acidic fractions of human breast milk. The aim of this study was to determine whether the two components would form a bioactive complex during simulated gastric (GI) transit. Results showed that a complex consisting of α-LA and OA is formed as the protein unfolds under acidic conditions and subsequently refolds upon pH increase. Analysis of this complex using Nuclear Magnetic Resonance and Fourier Transform Infra-Red (FTIR) spectroscopies estimated a stoichiometry of 4.1 and 4.4 oleic acids per mole of protein, respectively. FTIR and fluorescence spectroscopies showed that the structure was similar to that of BAMLET. Cytotoxicity testing against cancer cell line U937 cells showed that the complex had an LC50 value of 14.08 μM compared to 9.15 μM for BAMLET. These findings suggest that a BAMLET-like complex may be formed under the tested in vitro GI conditions.

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Abbreviations

BAMLET:

BAMLET produced through chromatography

α-LA:

Holo α-LA at pH 7

Gastric α-LA:

Partially digested α-LA in the gastric phase at pH 2.5

Post-gastric α-LA:

Partially digested α-LA after increase to pH 7

OA:

Oleic acid

FTIR:

Fourier transform infra-red spectroscopy

NMR:

Nuclear magnetic resonance

ANS:

8-Anilino-1-naphthanene sulphonate

BSSL:

Bile salt-stimulated lipase

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Acknowledgments

This work was funded under the Food Institute Management Research project number 08RDTMFRC650. Louise Sullivan was funded under the Teagasc Walsh Fellowship scheme. This work was carried out in conjunction with COST Action FA 1005, Infogest. Louise Sullivan was sponsored with a travel grant by this action. The authors wish to thank Dr John O’Brien and Dr Alan Hennessey for their technical assistance.

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Authors and Affiliations

  1. Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland

    Louise M. Sullivan & André Brodkorb

  2. Trinity Biomedical Sciences Institute (TBSI), School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland

    Louise M. Sullivan & K. Hun Mok

  3. Trinity College Dublin, Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Dublin 2, Ireland

    K. Hun Mok

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  1. Louise M. Sullivan
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  2. K. Hun Mok
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Correspondence to André Brodkorb.

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Sullivan, L.M., Mok, K.H. & Brodkorb, A. The Formation of an Anti-Cancer Complex Under Simulated Gastric Conditions. Food Dig. 4, 7–18 (2013). https://doi.org/10.1007/s13228-012-0030-0

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