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Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models
- 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 alsoAlkylphospholipids 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.…
Verfasserangaben: | Rumiana TzonevaORCiDGND, Tihomira StoyanovaORCiD, Annett PetrichORCiDGND, Desislava Popova, Veselina UzunovaORCiD, Momchilova AlbenaORCiD, Salvatore ChiantiaORCiDGND |
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URN: | urn:nbn:de:kobv:517-opus4-477056 |
DOI: | https://doi.org/10.25932/publishup-47705 |
ISSN: | 1866-8372 |
Titel des übergeordneten Werks (Deutsch): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1000) |
Publikationstyp: | Postprint |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 23.09.2020 |
Erscheinungsjahr: | 2020 |
Veröffentlichende Institution: | Universität Potsdam |
Datum der Freischaltung: | 23.09.2020 |
Freies Schlagwort / Tag: | alkylphospholipids; cancer; fluorescence correlation spectroscopy; fluorescence microscopy; lipids; lipid–lipid interactions; membrane biophysics; membrane microdomains; plasma membrane |
Ausgabe: | 1000 |
Seitenanzahl: | 19 |
Quelle: | Biomolecules 10 (2020) 5, 802 DOI: 10.3390/biom10050802 |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer Review: | Referiert |
Publikationsweg: | Open Access / Green Open-Access |
Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
Externe Anmerkung: | Bibliographieeintrag der Originalveröffentlichung/Quelle |