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Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein.
The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lam...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1996
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074716/ https://www.ncbi.nlm.nih.gov/pubmed/8795567 |
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author | Quesada, A. R. García Grávalos, M. D. Fernández Puentes, J. L. |
author_facet | Quesada, A. R. García Grávalos, M. D. Fernández Puentes, J. L. |
author_sort | Quesada, A. R. |
collection | PubMed |
description | The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lamellarins were performed on a panel of tumour cell lines, including two multidrug-resistant cell lines. Some lamellarins showed good anti-tumour activity, with similar levels of cytotoxicity against both the resistant and their corresponding parental cell lines. Two lamellarins displayed a high potency against lung carcinoma cells. Studies of the resistance modifier activity of the different lamellarins at non-toxic concentrations were also carried out in cells exhibiting MDR, and lamellarin I was selected for the highest chemosensitising activity. At non-toxic doses, verapamil and lamellarin I effectively increased the cytotoxicity of doxorubicin, vinblastine and daunorubicin in a concentration-dependent manner in multidrug-resistant cells, but the potency of lamellarin I as a MDR modulator was 9- to 16-fold higher than that of verapamil. In vitro measurements of rhodamine 123 accumulation in the multidrug-resistant Lo Vo/Dx cells suggest that lamellarin I reverses MDR by directly inhibiting the P-gp-mediated drug efflux. This work underscores the possibility of using these marine-derived compounds as a potential new source of anti-tumoral drugs active on resistant cells as well as of non-toxic modulators of the MDR phenotype. |
format | Text |
id | pubmed-2074716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1996 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20747162009-09-10 Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. Quesada, A. R. García Grávalos, M. D. Fernández Puentes, J. L. Br J Cancer Research Article The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lamellarins were performed on a panel of tumour cell lines, including two multidrug-resistant cell lines. Some lamellarins showed good anti-tumour activity, with similar levels of cytotoxicity against both the resistant and their corresponding parental cell lines. Two lamellarins displayed a high potency against lung carcinoma cells. Studies of the resistance modifier activity of the different lamellarins at non-toxic concentrations were also carried out in cells exhibiting MDR, and lamellarin I was selected for the highest chemosensitising activity. At non-toxic doses, verapamil and lamellarin I effectively increased the cytotoxicity of doxorubicin, vinblastine and daunorubicin in a concentration-dependent manner in multidrug-resistant cells, but the potency of lamellarin I as a MDR modulator was 9- to 16-fold higher than that of verapamil. In vitro measurements of rhodamine 123 accumulation in the multidrug-resistant Lo Vo/Dx cells suggest that lamellarin I reverses MDR by directly inhibiting the P-gp-mediated drug efflux. This work underscores the possibility of using these marine-derived compounds as a potential new source of anti-tumoral drugs active on resistant cells as well as of non-toxic modulators of the MDR phenotype. Nature Publishing Group 1996-09 /pmc/articles/PMC2074716/ /pubmed/8795567 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Quesada, A. R. García Grávalos, M. D. Fernández Puentes, J. L. Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title | Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title_full | Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title_fullStr | Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title_full_unstemmed | Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title_short | Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. |
title_sort | polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by p-glycoprotein. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074716/ https://www.ncbi.nlm.nih.gov/pubmed/8795567 |
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