The Alpha-Lactalbumin/Oleic Acid Complex and Its Cytotoxic Activity

Jøhnke, Marcel; Petersen, Torben E.

doi:10.5772/48184

Cited by 12 publications

(16 citation statements)

References 124 publications

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“…While studies showing selective killing of cancer cells by BAMLET are numerous [1,4,33,34], recent reports suggest that the OA complex of α-LA may also be toxic to some non-cancerous cell, human erythrocytes [17] as well as to antibiotic sensitive and resistant strains of Streptococcus pnuemoniae [35,36]. Figure 2A shows that in addition to human erythrocytes, those derived from several other mammals were readily hemolyzed by BAMLET, although their sensitivity to the α-LA-OA complex varied.…”

Section: Resultsmentioning

confidence: 99%

“…Evidence for the penetration of HAMLET/BAMLET into tumor cells and attack on several critical organalles including mitochondria, endoplasmic reticulum, proteasomes, lysosomes and trigger cell death pathways are available [9,34,53]. Storm et al [11] observed that that c-Myc oncogene is an important determinant of HAMLET sensitivity; cells expressing high levels of the c-Myc gene were more sensitive while knock down of the gene lowered HAMLET sensitivity and modified the glycolytic state of the cells.…”

Section: Resultsmentioning

confidence: 99%

“…The in vivo interaction of Alexa Fluor 568-labelled HAMLET with hexokinase1 using confocal microscopy as well as direct binding to the enzyme in vitro with the help of a high functional protein array has also been taken as evidence in support of the tumoricidal role of α-LA in the HAMLET [11]. A recent review has also summarized the potential role of the partially unfolded protein in HAMLET/BAMLET-like complexes [34]. Puthia et al [13], in a more recent study have shown that HAMLET acts by triggering a Wnt-independent and ion channel dependent mechanism controlling β-catenin level in addition to the effects on β-catenin signalling.…”

Section: Resultsmentioning

confidence: 99%

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Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

et al. 2013

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A chance discovery of the tumoricidal action of a human milk fraction led to the characterization of the active component as oleic acid complex of the α-lactalbumin, which was given the acronym HAMLET. We report in this study that the oleic acid complex of bovine α-lactalbumin (BAMLET) is hemolytic to human erythrocytes as well as to those derived from some other mammals. Indirect immunofluorescence analysis suggested binding of BAMLET to erythrocytes prior to induction of hemolysis. Free OA was hemolytic albeit at higher concentrations, while sodium oleate caused hemolysis at far lower concentrations. Amiloride and BaCl2 offered protection against BAMLET-induced hemolysis suggesting the involvement of a cation leak channel in the process. BAMLET coupled to CNBr-activated Sepharose was not only hemolytic but also tumoricidal to Jurkat and MCF-7 cells in culture. The Sepharose-linked preparation was however not toxic to non-cancerous peritoneal macrophages and primary adipocytes. The tumoricidal action was studied using the MTT-assay while apoptosis induction measured by the annexin V-propidium iodide assay. Repeated incubation of the immobilized BAMLET with erythrocytes depleted oleic acid and decreased the hemolytic activity of the complex. Incubation of MCF-7 and Jurkat cells with OA, soluble or immobilized BAMLET resulted in increase in the uptake of Lyso Tracker Red and Nile red by the cells. The data presented support the contention that oleic acid plays the key role, both in BAMLET-induced hemolysis and tumoricidal action.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

et al. 2013

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“…2). The α-La/oleic acid complex and its cytotoxic activity was reviewed by Jøhnke and Petersen (2012). α-La, a unique milk protein, is homologous with c-type lysozymes.…”

Section: Bioactivity Of α-Lactalbuminmentioning

confidence: 99%

Dairy Chemistry and Biochemistry

Fox¹,

Uniacke‐Lowe²,

McSweeney³

et al. 2015

568

570

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“…oleic acid), it induced selective apoptosis in tumoural and immature tumour cells, but not in healthy differentiated cells (Spolaore et al 2010;Barbana et al 2011). However, the exact mechanisms are still unclear (Johnke and Petersen 2012).…”

Section: Introductionmentioning

confidence: 99%

Safety of milk‐derived bioactive peptides

Beltrán-Barrientos

Garcı́a

Torres-Llanez

et al. 2016

Int J of Dairy Tech

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Bioactive milk peptides are protein fragments with potential biological activities. Over the past decades, studies have mainly focused on the health benefits of these bioactive peptides; however, only a few studies have evaluated their safety. In this review, we describe the scientific literature regarding their effects on both cell lines and on animal and human models, in terms of allergenicity, cytotoxicity, genotoxicity and mutagenicity.

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The Alpha-Lactalbumin/Oleic Acid Complex and Its Cytotoxic Activity

Cited by 12 publications

References 124 publications

Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

Dairy Chemistry and Biochemistry

Safety of milk‐derived bioactive peptides

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