Note: Apoptosis induced by a human milk protein
Note: Apoptosis induced by a human milk protein
Overall
Human milk is surprisingly beneficial for killing cancer cells.
Analysis of this effect revealed that a component of milk in a particular physical state-multimeric a-lactalbumin-is a potent Ca2+-elevating and apoptosis-inducing agent with broad (selective in some extent) cytotoxic activity.
Multimeric alpha lactabumin
Killed
transformed cells
Embryonic cells
Lymphoid cells
Not kill
Mature epithelial cells
Thus, they mentioned that human milk not only contain the ability to kill microbes but maintain the function of lymphocytes and epithelium (I think they mean to keep the balance between two populations -- lymphocytes and epithelial cells)
Analysing the cytotoxic mechanism aids to design antitumor agents.
From the experiments; they noticed that the components within the breast milk can change the morphology of transformed cells which look like apoptosis.
Active component was later identified as multimeric alpha-lactalbumin (MAL)
Induce apoptosis in
Variety of transformed cells
Immature mammalian cells
Component;
Human alpha lactalbumin
Bovine serum albumin
Human lysozyme
Chicken lysozyme
Human lactoferrin
Cycloheximide
Cells;
A549
NCI-H292
A-498
J82
CaCO2
HT29
5637
GMK -- normal monkey cells
Vero -- normal monkey cells
MDCK -- normal carnis cells
B9
WEHI164
Cell viability was measured by trypan blue and thymidine consumption
Human milk kills
Transformed cell lines
Non-transformed immature cell lines
Lymphoid cells
Human milk not kill
Mature cells
Alpha-lactalbumin
Monomer not toxic
Multimeric (MAL) form (after passing through ion-exchange column -- which containing salt) -- become toxic
Focusing on MAL
Human milk -- > fractionation -- > casein fraction induces apoptosis in many cell lines -- > later identified the active component as multimeric form of alpha-lactalbumin -- > clarified more on specificity -- > kill only transformed/non-transformed immature cell line but not kill non-transformed mature cell line
They proposed;
being in an aggregated state, MAL might possibly form transmembrane pores and evoke apoptosis by allowing the influx of Ca2+ and other solutes.
The potency and selectivity of the apoptosis-inducing activity of MAL lead us to suggest that it may act to restrict certain host cell populations.
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