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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-12

AUTHORS

Marilena Celano, Maria Grazia Calvagno, Stefania Bulotta, Donatella Paolino, Franco Arturi, Domenicoantonio Rotiroti, Sebastiano Filetti, Massimo Fresta, Diego Russo

ABSTRACT

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 microM, 7 fold at 100 microM). 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 microM) 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. More... »

PAGES

63

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-4-63

DOI

http://dx.doi.org/10.1186/1471-2407-4-63

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039966710

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15363094


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38 schema: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 microM, 7 fold at 100 microM). 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 microM) 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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