Note: Apoptosis induced by a human milk protein

Note: Apoptosis induced by a human milk protein

Doi: 10.1073/pnas.92.17.8064


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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