Apoptosis induced by a human milk protein

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Apoptosis induced by a human milk protein. / Håkansson, Anders P; Zhivotovsky, B; Orrenius, S; Sabharwal, H; Svanborg, C.

In: Proceedings of the National Academy of Sciences, Vol. 92, No. 17, 15.08.1995, p. 8064-8068.

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Håkansson, Anders P ; Zhivotovsky, B ; Orrenius, S ; Sabharwal, H ; Svanborg, C. / Apoptosis induced by a human milk protein. In: Proceedings of the National Academy of Sciences. 1995 ; Vol. 92, No. 17. pp. 8064-8068.

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TY - JOUR

T1 - Apoptosis induced by a human milk protein

AU - Håkansson, Anders P

AU - Zhivotovsky, B

AU - Orrenius, S

AU - Sabharwal, H

AU - Svanborg, C

PY - 1995/8/15

Y1 - 1995/8/15

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Bacterial Adhesion

KW - Breast Feeding

KW - Calcium

KW - Calcium-Transporting ATPases

KW - Cattle

KW - Cell Line

KW - Cell Survival

KW - Chromatin

KW - Chromatography, Ion Exchange

KW - Dogs

KW - Electrophoresis, Polyacrylamide Gel

KW - Embryo, Mammalian

KW - Female

KW - Humans

KW - Infant

KW - Lactalbumin

KW - Lung Neoplasms

KW - Lymphocytes

KW - Milk Proteins

KW - Milk, Human

KW - Terpenes

KW - Thapsigargin

KW - Tumor Cells, Cultured

U2 - 10.1073/pnas.92.17.8064

DO - 10.1073/pnas.92.17.8064

M3 - Article

VL - 92

SP - 8064

EP - 8068

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 17

ER -