IEC-6 Intestinal Cell Death Induced by Bovine Milk α-Lactalbumin

Xu, Meiyu; Sugiura, Yoshimasa; Nagaoka, Satoshi; Kanamaru, Yoshihiro

doi:10.1271/bbb.69.1082

Cited by 26 publications

(31 citation statements)

References 28 publications

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“…The potent toxicity of free oleic acid against Jurkat and HL-60 tumor cells has been shown, supporting the proposal that the fatty acid could be the cytotoxic component of the HAMLET complex [54,55]. However, in contrast with this proposal, -LA has previously been found to be cytotoxic in the absence of oleic acid [56][57][58][59][60].…”

Section: Characteristics Of Hamletsupporting

confidence: 55%

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

Jøhnke¹,

Petersen²

2012

Milk Protein

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Section: Characteristics Of Hamletsupporting

confidence: 55%

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

Jøhnke¹,

Petersen²

2012

Milk Protein

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“…6) -LA, treatment with 30% 2,2,2-trifluoroethanol (TFE) exhibited cytotoxicity to IEC-6 cells. 1) This report indicated that a certain SDS-stable higher molecular state might be implicated in the cytotoxicity of bovine -LA, as well as another reports 1,7) but, the exact character of the higher Mr cytotoxic forms of bovine -LA was left unclear, and the structure of -LA with toxicity was not discussed. Co-solvent TFE is often used to aid the formation of secondary structure in solution in solution peptides, or alternately as a denaturant in protein folding studies.…”

mentioning

confidence: 87%

“…2,3) The acid state of -LA at low pH values, the classical molten globule state, has been confirmed. 4) We have reported that monomeric 14-kDa bovine -LA showed a stimulatory effect rather than an inhibitory one on the proliferation of a cultured IEC-6 cell line, 1) since the intestinal epithelial cell line IEC-6 consists of nontumor cells from the rat crypt, maintains growth ability, and displays phenotypes of undifferentiated cells in passage culture. 5) IEC-6 cells have been used in numerous studies to elucidate the mechanisms of differentiation, cellular growth, wound healing, and growth regulation by autocrine and paracrine.…”

mentioning

confidence: 99%

Comparison of the Efficacy of Alpha-Lactalbumin from Equine, Bovine, and Human Milk in the Growth of Intestinal IEC-6 Cells

Xijier¹,

Mori

Fukuoka

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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Native alpha-lactalbumins (α-LA) from equine, bovine, and human milk were not cytotoxic. However, after treatment with trifluoroethanol (TFE), all three α-LAs exhibited cytotoxicity. Toxic potencies were distinctly different among them. Equine α-LA was the most robust, bovine α-LA was moderate, and human α-LA was weak. There were no significant structural changes as between the native and the TFE-treated α-LAs.

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“…There is evidence that α-lactalbumin triggers apoptosis of mammary cells during weaning, as the regulatory mechanism for breast involution when milk is no longer needed (62). Alpha-lactalbumin protein triggers cell death in normal rat intestinal epithelial cells (63) and virus-transformed mouse leukaemia cells (64). These results and HAMLET results showing HAMLET cytotoxicity superior to that of the oleic acid alone (3)(4)(5)15,17,38,44,50,54), indicate that α-lactalbumin protein is also playing role in HAMLET-induced cell death.…”

Section: Oleic Acid Is the Main Active Componentmentioning

confidence: 99%

Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components

et al. 2015

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-The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLETlike compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified.

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IEC-6 Intestinal Cell Death Induced by Bovine Milk α-Lactalbumin

Cited by 26 publications

References 28 publications

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

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

Comparison of the Efficacy of Alpha-Lactalbumin from Equine, Bovine, and Human Milk in the Growth of Intestinal IEC-6 Cells

Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components

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