Calcium electroporation and electrochemotherapy for cancer treatment

Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy

K.L. Hoejholt, T. Muzic, S.D. Jensen, Louise Torp Dalgaard, M. Bilgin, J. Nylandsted, T. Heimburg, S.K. Frandsen, J Gehl

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.
Original languageEnglish
Article number4758
JournalScientific Reports
Volume2019
Issue number9
ISSN2045-2322
DOIs
Publication statusPublished - 2019

Cite this

Hoejholt, K.L. ; Muzic, T. ; Jensen, S.D. ; Dalgaard, Louise Torp ; Bilgin, M. ; Nylandsted, J. ; Heimburg, T. ; Frandsen, S.K. ; Gehl, J. / Calcium electroporation and electrochemotherapy for cancer treatment : Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy. In: Scientific Reports. 2019 ; Vol. 2019, No. 9.
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title = "Calcium electroporation and electrochemotherapy for cancer treatment: Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy",
abstract = "Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.",
author = "K.L. Hoejholt and T. Muzic and S.D. Jensen and Dalgaard, {Louise Torp} and M. Bilgin and J. Nylandsted and T. Heimburg and S.K. Frandsen and J Gehl",
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Calcium electroporation and electrochemotherapy for cancer treatment : Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy. / Hoejholt, K.L.; Muzic, T.; Jensen, S.D.; Dalgaard, Louise Torp; Bilgin, M.; Nylandsted, J. ; Heimburg, T. ; Frandsen, S.K.; Gehl, J.

In: Scientific Reports, Vol. 2019, No. 9, 4758, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Calcium electroporation and electrochemotherapy for cancer treatment

T2 - Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy

AU - Hoejholt, K.L.

AU - Muzic, T.

AU - Jensen, S.D.

AU - Dalgaard, Louise Torp

AU - Bilgin, M.

AU - Nylandsted, J.

AU - Heimburg, T.

AU - Frandsen, S.K.

AU - Gehl, J

PY - 2019

Y1 - 2019

N2 - Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.

AB - Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.

U2 - 10.1038/s41598-019-41188-z

DO - 10.1038/s41598-019-41188-z

M3 - Journal article

VL - 2019

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 9

M1 - 4758

ER -