Document Detail


Anticancer effects of fenretinide in human medulloblastoma.
MedLine Citation:
PMID:  16399227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C Damodar Reddy; Asha Guttapalli; Peter C Adamson; Mohan C Vemuri; Donald O'Rourke; Leslie N Sutton; Peter C Phillips
Related Documents :
17922917 - Erwinia carotovora elicitors and botrytis cinerea activate defense responses in physcom...
20528917 - The silencing of adenine nucleotide translocase isoform 1 induces oxidative stress and ...
17261067 - 20s-protopanaxadiol-induced programmed cell death in glioma cells through caspase-depen...
11890677 - Fenton reaction is primarily involved in a mechanism of (-)-epigallocatechin-3-gallate ...
14657177 - Genetic control of interconnected neuronal populations in the mouse primary visual system.
1920017 - Human periodontal cells initiate mineral-like nodules in vitro.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  231     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-09     Completed Date:  2006-03-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  262-9     Citation Subset:  IM    
Affiliation:
Division of Neuro-Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. reddyd@email.chop.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / 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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-...
Next Document:  Alisol B acetate, a triterpene from Alismatis rhizoma, induces Bax nuclear translocation and apoptos...