Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models.
alkylphospholipids
cancer
fluorescence correlation spectroscopy
fluorescence microscopy
lipids
lipid–lipid interactions
membrane biophysics
membrane microdomains
plasma membrane
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
22 05 2020
22 05 2020
Historique:
received:
02
04
2020
revised:
15
05
2020
accepted:
19
05
2020
entrez:
28
5
2020
pubmed:
28
5
2020
medline:
7
4
2021
Statut:
epublish
Résumé
Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid-lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.
Identifiants
pubmed: 32455962
pii: biom10050802
doi: 10.3390/biom10050802
pmc: PMC7277205
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Lipid Bilayers
0
Membrane Lipids
0
Organophosphates
0
Quaternary Ammonium Compounds
0
erucylphospho-N,N,N-trimethylpropylammonium
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bulgarian National Science Fund
ID : DN 11/1/2017
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : 254850309
Pays : International
Organisme : Scientific Infrastructure on Cell Technologies in Biomedicine
ID : DО1-154/28/08/2018/
Pays : International
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