| Anticancer effects of fenretinide in human medulloblastoma. | |
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MedLine Citation:
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PMID: 16399227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) a synthetic retinoid is in clinical trials for the treatment of several malignancies. However, its biological effects and therapeutic value in childhood brain tumor medulloblastoma (MB) has not been investigated. In this study, we report for the first time that fenretinide (2.5-10 microM) induces apoptotic cell death in human MB cells. We observed significant inhibition of cell survival in four MB cell lines (D425MED, D458MED, D283MED and D341MED) as determined by MTT assays. These results were further supported by inhibition of anchorage-independent colony formation in soft agar. Fenretinide-induced decrease in cell viability was in part due to activation of caspase-3 dependent cell death, which was further supported by the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a caspase-3 substrate. Cell death was partially prevented by the antioxidant, l-ascorbic acid suggesting that free radical intermediates might be involved in fenretinide effects. These results suggest that pharmacologically achievable concentrations of fenretinide are effective in killing MB cells and thus show its therapeutic potential to treat human MB. |
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Authors:
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C Damodar Reddy; Asha Guttapalli; Peter C Adamson; Mohan C Vemuri; Donald O'Rourke; Leslie N Sutton; Peter C Phillips |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer letters Volume: 231 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2006 Jan |
Date Detail:
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Created Date: 2006-01-09 Completed Date: 2006-03-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 262-9 Citation Subset: IM |
Affiliation:
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Division of Neuro-Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. reddyd@email.chop.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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therapeutic use* Antioxidants / pharmacology Apoptosis / drug effects Ascorbic Acid / pharmacology Caspase 3 Caspases / metabolism Cell Proliferation / drug effects Cerebellar Neoplasms / drug therapy*, metabolism, pathology Enzyme Activation / drug effects Fenretinide / therapeutic use* Humans Medulloblastoma / drug therapy*, metabolism, pathology Poly(ADP-ribose) Polymerases / metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Antioxidants; 50-81-7/Ascorbic Acid; 65646-68-6/Fenretinide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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