Document Detail


Dimethylfumarate impairs melanoma growth and metastasis.
MedLine Citation:
PMID:  17178886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To identify targets of DMF action, we analyzed mRNA expression in DMF-treated melanomas by gene chip arrays. Using BiblioSphere software for data analysis, significantly regulated genes were mapped to Gene Ontology terms cell death, cell growth, and cell cycle. Indeed, we found that DMF inhibited proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle was arrested at the G(2)-M boundary. Moreover, DMF was proapoptotic, as shown by cell cycle analysis and by Annexin V and Apo2.7 staining. These results were confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by Ki-67 immunostaining and increased apoptosis as assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining. In conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth and metastasis in animal models.
Authors:
Robert Loewe; Teresa Valero; Silvia Kremling; Barbara Pratscher; Rainer Kunstfeld; Hubert Pehamberger; Peter Petzelbauer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-01-25     Revised Date:  2013-04-01    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11888-96     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / drug effects*
Cell Division / drug effects*
Cell Line, Tumor
Female
Fumarates / therapeutic use*
Humans
Lymphatic Metastasis / pathology,  prevention & control
Melanoma / genetics,  pathology*
Mice
Mice, Inbred C57BL
Neoplasm Metastasis / prevention & control*
Radiation-Sensitizing Agents / therapeutic use*
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Fumarates; 0/Radiation-Sensitizing Agents; FO2303MNI2/dimethyl fumarate

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


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