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Sulindac and its metabolites: Sulindac sulfide and sulindac sulfone enhance cytotoxic effects of arsenic trioxide on leukemic cell lines.
MedLine Citation:
PMID:  21515355     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200μM) with SS being the most cytotoxic (72h WST-1 reduction test). The cytotoxicity of ATO was enhanced by combination with sulindacs. The combination of ATO (1μM) with SS or SF at concentrations over 50μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48h to the combinations showed smaller decrease in viability. Measurements of Jurkat, HL-60 and K562 cells exposed to ATO (1μM) and sulindacs (100μM or 200μM for K562 cells) indicated apoptosis as the main cell death mechanism. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.
Authors:
Maciej Stępnik; Magdalena Ferlińska; Anna Smok-Pieniążek; Dobrosława Gradecka-Meesters; Joanna Arkusz; Małgorzata Stańczyk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-15
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  -     ISSN:  1879-3177     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Sw. Teresy St., 91 348 Łódź, Poland.
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