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Apoptosis induced by a human milk protein

Håkansson, Anders P LU orcid ; Zhivotovsky, B ; Orrenius, S ; Sabharwal, H and Svanborg, C LU (1995) In Proceedings of the National Academy of Sciences 92(17). p.8064-8068
Abstract

To the breast-fed infant, human milk is more than a source of nutrients; it furnishes a wide array of molecules that restrict microbes, such as antibodies, bactericidins, and inhibitors of bacterial adherence. However, it has rarely been considered that human milk may also contain substances bioactive toward host cells. While investigating the effect of human milk on bacterial adherence to a human lung cancer cell line, we were surprised to discover that the milk killed the cells. Analysis of this effect revealed that a component of milk in a particular physical state--multimeric alpha-lact-albumin--is a potent Ca(2+)-elevating and apoptosis-inducing agent with broad, yet selective, cytotoxic activity. Multimeric alpha-lactalbumin... (More)

To the breast-fed infant, human milk is more than a source of nutrients; it furnishes a wide array of molecules that restrict microbes, such as antibodies, bactericidins, and inhibitors of bacterial adherence. However, it has rarely been considered that human milk may also contain substances bioactive toward host cells. While investigating the effect of human milk on bacterial adherence to a human lung cancer cell line, we were surprised to discover that the milk killed the cells. Analysis of this effect revealed that a component of milk in a particular physical state--multimeric alpha-lact-albumin--is a potent Ca(2+)-elevating and apoptosis-inducing agent with broad, yet selective, cytotoxic activity. Multimeric alpha-lactalbumin killed all transformed, embryonic, and lymphoid cells tested but spared mature epithelial elements. These findings raise the possibility that milk contributes to mucosal immunity not only by furnishing antimicrobial molecules but also by policing the function of lymphocytes and epithelium. Finally, analysis of the mechanism by which multimeric alpha-lactalbumin induces apoptosis in transformed epithelial cells could lead to the design of antitumor agents.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Apoptosis, Bacterial Adhesion, Breast Feeding, Calcium, Calcium-Transporting ATPases, Cattle, Cell Line, Cell Survival, Chromatin, Chromatography, Ion Exchange, Dogs, Electrophoresis, Polyacrylamide Gel, Embryo, Mammalian, Female, Humans, Infant, Lactalbumin, Lung Neoplasms, Lymphocytes, Milk Proteins, Milk, Human, Terpenes, Thapsigargin, Tumor Cells, Cultured
in
Proceedings of the National Academy of Sciences
volume
92
issue
17
pages
5 pages
publisher
National Academy of Sciences
external identifiers
  • pmid:7644538
  • scopus:0029155831
ISSN
0027-8424
DOI
10.1073/pnas.92.17.8064
language
English
LU publication?
yes
id
6223dc5d-81dc-4dc0-880a-0e582b2b221a
date added to LUP
2016-05-21 11:34:47
date last changed
2024-01-04 04:15:31
@article{6223dc5d-81dc-4dc0-880a-0e582b2b221a,
  abstract     = {{<p>To the breast-fed infant, human milk is more than a source of nutrients; it furnishes a wide array of molecules that restrict microbes, such as antibodies, bactericidins, and inhibitors of bacterial adherence. However, it has rarely been considered that human milk may also contain substances bioactive toward host cells. While investigating the effect of human milk on bacterial adherence to a human lung cancer cell line, we were surprised to discover that the milk killed the cells. Analysis of this effect revealed that a component of milk in a particular physical state--multimeric alpha-lact-albumin--is a potent Ca(2+)-elevating and apoptosis-inducing agent with broad, yet selective, cytotoxic activity. Multimeric alpha-lactalbumin killed all transformed, embryonic, and lymphoid cells tested but spared mature epithelial elements. These findings raise the possibility that milk contributes to mucosal immunity not only by furnishing antimicrobial molecules but also by policing the function of lymphocytes and epithelium. Finally, analysis of the mechanism by which multimeric alpha-lactalbumin induces apoptosis in transformed epithelial cells could lead to the design of antitumor agents.</p>}},
  author       = {{Håkansson, Anders P and Zhivotovsky, B and Orrenius, S and Sabharwal, H and Svanborg, C}},
  issn         = {{0027-8424}},
  keywords     = {{Animals; Apoptosis; Bacterial Adhesion; Breast Feeding; Calcium; Calcium-Transporting ATPases; Cattle; Cell Line; Cell Survival; Chromatin; Chromatography, Ion Exchange; Dogs; Electrophoresis, Polyacrylamide Gel; Embryo, Mammalian; Female; Humans; Infant; Lactalbumin; Lung Neoplasms; Lymphocytes; Milk Proteins; Milk, Human; Terpenes; Thapsigargin; Tumor Cells, Cultured}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{17}},
  pages        = {{8064--8068}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Apoptosis induced by a human milk protein}},
  url          = {{http://dx.doi.org/10.1073/pnas.92.17.8064}},
  doi          = {{10.1073/pnas.92.17.8064}},
  volume       = {{92}},
  year         = {{1995}},
}