Document Detail


Comparative activity of melarsoprol and arsenic trioxide in chronic B-cell leukemia lines.
MedLine Citation:
PMID:  9226155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inorganic arsenic trioxide (As2O3) was recently shown to induce apoptosis in NB4 promyelocytic leukemic cells. We have investigated the effects of the organic arsenical, melarsoprol (a drug used for treatment of trypanosomiasis), upon induction of apoptosis in cell lines representative of chronic B-cell lymphoproliferative disorders. An Epstein-Barr virus (EBV)-transformed B-prolymphocytic cell line (JVM-2), an EBV-transformed B-cell chronic lymphocytic leukemia (B-CLL) cell line (I83CLL), and one non-EBV-transformed B-CLL cell line (WSU-CLL) were used as targets. Dose-response experiments with melarsoprol (10(-7) to 10(-9) mol/L) were performed over 96 hours. Unexpectedly, we found that melarsoprol caused a dose- and time-dependent inhibition of survival and growth in all three cell lines. In contrast, As2O3 at similar concentrations had no effect on either viability or growth. After 24 hours, all three cell lines treated with melarsoprol (10(-7) mol/L) exhibited morphologic characteristics of apoptosis. We also observed prominent concentration-dependent downregulation of bcl-2 mRNA after 24 hours of exposure to melarsoprol in WSU-CLL, I83CLL, and JVM-2 cells. Decrease of bcl-2 protein expression was also observed in all three cell lines, whereas As2O3 had no effect on this parameter. We conclude that melarsoprol may inhibit the growth of lymphoid leukemic cell by promoting programmed cell death. Results of these studies suggest that melarsoprol shows promising therapeutic activity in these diseases, and a study to evaluate clinical effects of this drug has been initiated.
Authors:
A König; L Wrazel; R P Warrell; R Rivi; P P Pandolfi; A Jakubowski; J L Gabrilove
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  90     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-08-07     Completed Date:  1997-08-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  562-70     Citation Subset:  AIM; IM    
Affiliation:
Sloan-Kettering Institute, the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / toxicity*
Apoptosis / drug effects
Arsenic Poisoning*
Arsenicals*
Cell Division / drug effects
Cell Line, Transformed
Cell Survival / drug effects
DNA Damage
DNA Fragmentation
Drug Screening Assays, Antitumor
Herpesvirus 4, Human
Humans
Kinetics
Leukemia, Lymphocytic, Chronic, B-Cell
Melarsoprol / toxicity*
Oxides / toxicity*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
RNA, Messenger / biosynthesis
Time Factors
Transcription, Genetic / drug effects
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arsenicals; 0/Oxides; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 1327-53-3/arsenic trioxide; 494-79-1/Melarsoprol
Comments/Corrections
Comment In:
Blood. 1992 Nov 15;80(10):2690-1   [PMID:  1294262 ]

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


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