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Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide
Doxorubicin, a widely used chemotherapeutic drug, has several potential high-risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652752/ https://www.ncbi.nlm.nih.gov/pubmed/29100358 http://dx.doi.org/10.18632/oncotarget.20217 |
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author | Øverbye, Anders Holsæter, Ann Mari Markus, Fusser Škalko-Basnet, Nataša Iversen, Tore-Geir Torgersen, Maria Lyngaas Sønstevold, Tonje Engebraaten, Olav Flatmark, Kjersti Mælandsmo, Gunhild Mari Skotland, Tore Sandvig, Kirsten |
author_facet | Øverbye, Anders Holsæter, Ann Mari Markus, Fusser Škalko-Basnet, Nataša Iversen, Tore-Geir Torgersen, Maria Lyngaas Sønstevold, Tonje Engebraaten, Olav Flatmark, Kjersti Mælandsmo, Gunhild Mari Skotland, Tore Sandvig, Kirsten |
author_sort | Øverbye, Anders |
collection | PubMed |
description | Doxorubicin, a widely used chemotherapeutic drug, has several potential high-risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study we have investigated the cytotoxic effect of doxorubicin encapsulated in liposomes with and without ceramides containing 6 or 12 carbon atoms in the N-amidated fatty acyl chains. The short-chain ceramide species were included in the liposomal compositions due to their pro-apoptotic properties, which might cause a synergistic anticancer effect. We demonstrate that the ceramide species enhance the liposomal doxorubicin toxicity in a cell-specific manner. The C6-ceramide effect is most pronounced in cervical cancer cells (HeLa) and colon cancer cells (HCT116), whereas the C12-ceramide effect is strongest in breast cancer cells (MDA-MB-231). Moreover, the study reveals the importance of investigating cell toxicity at several time points and in different cell-lines, to assess drug-and formulation-induced cytotoxic effects in vitro. Furthermore, our data show that the cytotoxicity obtained with the nanocarriers in vitro, does not necessarily reflect their ability to inhibit tumor growth in vivo. We speculate that the larger effect of Caelyx® than our liposomes in vivo is due to a greater in vivo stability of Caelyx®. |
format | Online Article Text |
id | pubmed-5652752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56527522017-11-02 Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide Øverbye, Anders Holsæter, Ann Mari Markus, Fusser Škalko-Basnet, Nataša Iversen, Tore-Geir Torgersen, Maria Lyngaas Sønstevold, Tonje Engebraaten, Olav Flatmark, Kjersti Mælandsmo, Gunhild Mari Skotland, Tore Sandvig, Kirsten Oncotarget Research Paper Doxorubicin, a widely used chemotherapeutic drug, has several potential high-risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study we have investigated the cytotoxic effect of doxorubicin encapsulated in liposomes with and without ceramides containing 6 or 12 carbon atoms in the N-amidated fatty acyl chains. The short-chain ceramide species were included in the liposomal compositions due to their pro-apoptotic properties, which might cause a synergistic anticancer effect. We demonstrate that the ceramide species enhance the liposomal doxorubicin toxicity in a cell-specific manner. The C6-ceramide effect is most pronounced in cervical cancer cells (HeLa) and colon cancer cells (HCT116), whereas the C12-ceramide effect is strongest in breast cancer cells (MDA-MB-231). Moreover, the study reveals the importance of investigating cell toxicity at several time points and in different cell-lines, to assess drug-and formulation-induced cytotoxic effects in vitro. Furthermore, our data show that the cytotoxicity obtained with the nanocarriers in vitro, does not necessarily reflect their ability to inhibit tumor growth in vivo. We speculate that the larger effect of Caelyx® than our liposomes in vivo is due to a greater in vivo stability of Caelyx®. Impact Journals LLC 2017-08-12 /pmc/articles/PMC5652752/ /pubmed/29100358 http://dx.doi.org/10.18632/oncotarget.20217 Text en Copyright: © 2017 Øverbye et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Øverbye, Anders Holsæter, Ann Mari Markus, Fusser Škalko-Basnet, Nataša Iversen, Tore-Geir Torgersen, Maria Lyngaas Sønstevold, Tonje Engebraaten, Olav Flatmark, Kjersti Mælandsmo, Gunhild Mari Skotland, Tore Sandvig, Kirsten Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title | Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title_full | Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title_fullStr | Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title_full_unstemmed | Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title_short | Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide |
title_sort | ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of c6 and c12 ceramide |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652752/ https://www.ncbi.nlm.nih.gov/pubmed/29100358 http://dx.doi.org/10.18632/oncotarget.20217 |
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