| Promising effects of the 4HPR-BSO combination in neuroblastoma monolayers and spheroids. | |
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MedLine Citation:
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PMID: 21741474 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10μM, 24h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100μM, 24h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capacity of each cell line and the increase in cytotoxicity induced by 4HPR-BSO compared to 4HPR. No significant correlation between baseline antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids, 4HPR-BSO induced a strong synergistic growth retardation and induction of apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in neuroblastoma monolayers and spheroids in ROS-producing cell lines. This indicates that the 4HPR-BSO combination might be a promising new strategy in the treatment of neuroblastoma. |
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Authors:
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Roos Cuperus; André B P van Kuilenburg; René Leen; Johannes Bras; Huib N Caron; Godelieve A M Tytgat |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-23 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-7-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Genetic Metabolic Diseases and Department of Pediatrics/Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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