| Influence of the level of gamma-glutamyltranspeptidase activity on the response of poorly and moderately differentiated rhabdomyosarcoma cell lines to all-trans-retinoic acid. | |
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MedLine Citation:
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PMID: 17075312 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Differentiation therapy with retinoic acid has been considered a potential approach for treating rhabdomyosarcoma. Analysis of retinoids as differentiating agents for rhabdomyosarcoma is, however, rendered incomplete by the fact that some rhabdomyosarcoma cell lines are retinoic acid resistant. Therefore, the aim of the present work was to study the effect of all-trans-retinoic acid on two rat tumour cell lines, derived from the same rhabdomyosarcoma tumour model (i.e. the moderately differentiated low metastatic F21 cell line and the poorly differentiated high metastatic S4MH cell line), to discover how degree of differentiation and glutathione metabolism influence response to this retinoic acid derivative. We observed that whereas in the S4MH cell line all-trans-retinoic acid induced a significant inhibition of tumorigenic potential, in F21 cells all-trans-retinoic acid enhanced tumour growth and only at a higher dose was there a slight antiproliferative effect. These effects were in consonance with the activity level of gamma-glutamyltranspeptidase, which was significantly increased in F21 cells, but not in S4MH cells, in response to the all-trans-retinoic acid-induced increase in reactive oxygen species. The pro-tumour effect observed in F21 cells was reversed by adding buthionine sulphoximide, a specific cellular glutathione-depleting agent, to the all-trans-retinoic acid treatment. This combination produced a decrease in gamma-glutamyltranspeptidase activity, and an increase in oxidative stress and apoptosis. Our findings suggest that the response to all-trans-retinoic-acid of the tumour cell lines studied is influenced by the strong relationship between intracellular glutathione content, gamma-glutamyltranspeptidase activity and degree of differentiation of the rhabdomyosarcoma cell line, and that this relationship should be taken into account when identifying 'retinoid-sensitive' tumours. |
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Authors:
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Teodoro Palomares; Begoña Castro; Maite del Olmo; Ainhoa Iglesias; Pedro Bilbao; Ana Alonso-Varona |
Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anti-cancer drugs Volume: 17 ISSN: 0959-4973 ISO Abbreviation: Anticancer Drugs Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-10-31 Completed Date: 2007-04-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
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Languages: eng Pagination: 1127-39 Citation Subset: IM |
Affiliation:
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Department of Surgery, Radiology and Physical Medicine, University of the Basque Country, Leioa, Vizcaya, Spain. teodoro.palomares@ehu.es |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology Apoptosis / drug effects Buthionine Sulfoximine / pharmacology Cell Differentiation / drug effects Cell Proliferation / drug effects Drug Combinations Female Glutathione / analysis Rats Rats, Wistar Reactive Oxygen Species / analysis Rhabdomyosarcoma / metabolism*, pathology* Transplantation, Homologous / pathology Tretinoin / pharmacology* Tumor Burden / drug effects Tumor Cells, Cultured gamma-Glutamyltransferase / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Drug Combinations; 0/Reactive Oxygen Species; 302-79-4/Tretinoin; 5072-26-4/Buthionine Sulfoximine; 70-18-8/Glutathione; EC 2.3.2.2/gamma-Glutamyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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