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Daniel Otzen

Liprotides kill cancer cells by disrupting the plasma membrane

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Liprotides kill cancer cells by disrupting the plasma membrane. / Frislev, Henriette S; Boye, Theresa Louise; Nylandsted, Jesper et al.

In: Scientific Reports, Vol. 7, 15129, 09.11.2017.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Frislev, HS, Boye, TL, Nylandsted, J & Otzen, D 2017, 'Liprotides kill cancer cells by disrupting the plasma membrane', Scientific Reports, vol. 7, 15129. https://doi.org/10.1038/s41598-017-15003-6

APA

Frislev, H. S., Boye, T. L., Nylandsted, J., & Otzen, D. (2017). Liprotides kill cancer cells by disrupting the plasma membrane. Scientific Reports, 7, [15129]. https://doi.org/10.1038/s41598-017-15003-6

CBE

Frislev HS, Boye TL, Nylandsted J, Otzen D. 2017. Liprotides kill cancer cells by disrupting the plasma membrane. Scientific Reports. 7:Article 15129. https://doi.org/10.1038/s41598-017-15003-6

MLA

Vancouver

Frislev HS, Boye TL, Nylandsted J, Otzen D. Liprotides kill cancer cells by disrupting the plasma membrane. Scientific Reports. 2017 Nov 9;7:15129. doi: 10.1038/s41598-017-15003-6

Author

Frislev, Henriette S ; Boye, Theresa Louise ; Nylandsted, Jesper et al. / Liprotides kill cancer cells by disrupting the plasma membrane. In: Scientific Reports. 2017 ; Vol. 7.

Bibtex

@article{8ae496164c4a424da63e2f6331a1d4d5,
title = "Liprotides kill cancer cells by disrupting the plasma membrane",
abstract = "HAMLET (human α-lactalbumin made lethal to tumour cells) is a complex of α-lactalbumin (aLA) and oleic acid (OA) which kills transformed cells, while leaving fully differentiated cells largely unaffected. Other protein-lipid complexes show similar anti-cancer potential. We call such complexes liprotides. The cellular impact of liprotides, while intensely investigated, remains unresolved. To address this, we report on the cell-killing mechanisms of liprotides prepared by incubating aLA with OA for 1 h at 20 or 80 °C (lip20 and lip80, respectively). The liprotides showed similar cytotoxicity against MCF7 cells, though lip80 acts more slowly, possibly due to intermolecular disulphide bonds formed during preparation. Liprotides are known to increase the fluidity of a membrane and transfer OA to vesicles, prompting us to focus on the effect of liprotides on the cell membrane. Extracellular Ca(2+) influx is important for activation of the plasma membrane repair system, and we found that removal of Ca(2+) from the medium enhanced the liprotides' killing effect. Liprotide cytotoxicity was also increased by knockdown of Annexin A6 (ANXA6), a protein involved in plasma membrane repair. We conclude that MCF7 cells counteract liprotide-induced membrane permeabilization by activating their plasma membrane repair system, which is triggered by extracellular Ca(2+) and involves ANXA6.",
keywords = "Journal Article",
author = "Frislev, {Henriette S} and Boye, {Theresa Louise} and Jesper Nylandsted and Daniel Otzen",
year = "2017",
month = nov,
day = "9",
doi = "10.1038/s41598-017-15003-6",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Liprotides kill cancer cells by disrupting the plasma membrane

AU - Frislev, Henriette S

AU - Boye, Theresa Louise

AU - Nylandsted, Jesper

AU - Otzen, Daniel

PY - 2017/11/9

Y1 - 2017/11/9

N2 - HAMLET (human α-lactalbumin made lethal to tumour cells) is a complex of α-lactalbumin (aLA) and oleic acid (OA) which kills transformed cells, while leaving fully differentiated cells largely unaffected. Other protein-lipid complexes show similar anti-cancer potential. We call such complexes liprotides. The cellular impact of liprotides, while intensely investigated, remains unresolved. To address this, we report on the cell-killing mechanisms of liprotides prepared by incubating aLA with OA for 1 h at 20 or 80 °C (lip20 and lip80, respectively). The liprotides showed similar cytotoxicity against MCF7 cells, though lip80 acts more slowly, possibly due to intermolecular disulphide bonds formed during preparation. Liprotides are known to increase the fluidity of a membrane and transfer OA to vesicles, prompting us to focus on the effect of liprotides on the cell membrane. Extracellular Ca(2+) influx is important for activation of the plasma membrane repair system, and we found that removal of Ca(2+) from the medium enhanced the liprotides' killing effect. Liprotide cytotoxicity was also increased by knockdown of Annexin A6 (ANXA6), a protein involved in plasma membrane repair. We conclude that MCF7 cells counteract liprotide-induced membrane permeabilization by activating their plasma membrane repair system, which is triggered by extracellular Ca(2+) and involves ANXA6.

AB - HAMLET (human α-lactalbumin made lethal to tumour cells) is a complex of α-lactalbumin (aLA) and oleic acid (OA) which kills transformed cells, while leaving fully differentiated cells largely unaffected. Other protein-lipid complexes show similar anti-cancer potential. We call such complexes liprotides. The cellular impact of liprotides, while intensely investigated, remains unresolved. To address this, we report on the cell-killing mechanisms of liprotides prepared by incubating aLA with OA for 1 h at 20 or 80 °C (lip20 and lip80, respectively). The liprotides showed similar cytotoxicity against MCF7 cells, though lip80 acts more slowly, possibly due to intermolecular disulphide bonds formed during preparation. Liprotides are known to increase the fluidity of a membrane and transfer OA to vesicles, prompting us to focus on the effect of liprotides on the cell membrane. Extracellular Ca(2+) influx is important for activation of the plasma membrane repair system, and we found that removal of Ca(2+) from the medium enhanced the liprotides' killing effect. Liprotide cytotoxicity was also increased by knockdown of Annexin A6 (ANXA6), a protein involved in plasma membrane repair. We conclude that MCF7 cells counteract liprotide-induced membrane permeabilization by activating their plasma membrane repair system, which is triggered by extracellular Ca(2+) and involves ANXA6.

KW - Journal Article

U2 - 10.1038/s41598-017-15003-6

DO - 10.1038/s41598-017-15003-6

M3 - Journal article

C2 - 29123177

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 15129

ER -