Document Detail


Organoammonium hydroselenites: antitumor action through radical balance regulation.
MedLine Citation:
PMID:  12681434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Organoammonium hydroselenites were synthesized and investigated as potential selective, anticancer prodrugs. These compounds were studied in vitro on human fibrosarcoma (HT-1080), hamster kidney endothelial (BHK 21) and normal mouse embryonic fibroblasts (NIH 3T3). Most of them were very active against HT-1080 (0.6-5.3 g/ml). Amino acid hydroselenites readily increased the nitric oxide (NO) concentration in the culture medium of HT-1080 cells (up to TG(100)=1500%); however, 4-amidohydroximinomethylpyridinium hydroselenite (TG(100)=24%) and o-phenanthrolinium hydroselenite (TG(100)=50%) were free radical inhibitors. All compounds were glutathione peroxidase inhibitors; some of them could also prevent hydrogen peroxide degradation by inhibition of catalase. The influence of the investigated ammonium hydroselenites on tumor cell (HT-1080) morphology was examined. The substances studied were also active in vivo against sarcoma S-180. The role of organoammonium hydroselenites as free radical regulators and their therapeutic antitumor are discussed.
Authors:
Pavel Arsenyan; Irina Shestakova; Kira Rubina; Ilona Domracheva; Alena Nesterova; Kristina Vosele; Olga Pudova; Edmunds Lukevics
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  465     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-08     Completed Date:  2004-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  229-35     Citation Subset:  IM    
Affiliation:
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia. pavel.arsenyan@lycos.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemical synthesis,  pharmacology*
Catalase / antagonists & inhibitors,  metabolism
Cell Line, Tumor
Cricetinae
Drug Screening Assays, Antitumor
Endothelium / drug effects,  physiology
Free Radicals / metabolism
Glutathione Peroxidase / antagonists & inhibitors,  metabolism
Mice
Organoselenium Compounds / chemical synthesis,  pharmacology*
Quaternary Ammonium Compounds / chemical synthesis,  pharmacology*
Sarcoma 180 / drug therapy
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Free Radicals; 0/Organoselenium Compounds; 0/Quaternary Ammonium Compounds; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase

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