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Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

BACKGROUND: Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. METHODS: In t...

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Autores principales: Celano, Marilena, Calvagno, Maria Grazia, Bulotta, Stefania, Paolino, Donatella, Arturi, Franco, Rotiroti, Domenicoantonio, Filetti, Sebastiano, Fresta, Massimo, Russo, Diego
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC517941/
https://www.ncbi.nlm.nih.gov/pubmed/15363094
http://dx.doi.org/10.1186/1471-2407-4-63
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author Celano, Marilena
Calvagno, Maria Grazia
Bulotta, Stefania
Paolino, Donatella
Arturi, Franco
Rotiroti, Domenicoantonio
Filetti, Sebastiano
Fresta, Massimo
Russo, Diego
author_facet Celano, Marilena
Calvagno, Maria Grazia
Bulotta, Stefania
Paolino, Donatella
Arturi, Franco
Rotiroti, Domenicoantonio
Filetti, Sebastiano
Fresta, Massimo
Russo, Diego
author_sort Celano, Marilena
collection PubMed
description BACKGROUND: Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. METHODS: In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. RESULTS: A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h). CONCLUSION: These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours.
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spelling pubmed-5179412004-09-24 Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells Celano, Marilena Calvagno, Maria Grazia Bulotta, Stefania Paolino, Donatella Arturi, Franco Rotiroti, Domenicoantonio Filetti, Sebastiano Fresta, Massimo Russo, Diego BMC Cancer Research Article BACKGROUND: Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. METHODS: In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. RESULTS: A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h). CONCLUSION: These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours. BioMed Central 2004-09-13 /pmc/articles/PMC517941/ /pubmed/15363094 http://dx.doi.org/10.1186/1471-2407-4-63 Text en Copyright © 2004 Celano et al; licensee BioMed Central Ltd.
spellingShingle Research Article
Celano, Marilena
Calvagno, Maria Grazia
Bulotta, Stefania
Paolino, Donatella
Arturi, Franco
Rotiroti, Domenicoantonio
Filetti, Sebastiano
Fresta, Massimo
Russo, Diego
Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title_full Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title_fullStr Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title_full_unstemmed Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title_short Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
title_sort cytotoxic effects of gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC517941/
https://www.ncbi.nlm.nih.gov/pubmed/15363094
http://dx.doi.org/10.1186/1471-2407-4-63
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