| Effects of the PAF-analog and -antagonist CV-6209 on cultured human glioma cell lines. | |
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MedLine Citation:
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PMID: 1886907 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell lines of human glioma (U-343 MGa and U-251 MG) and human glia (U-533 CG) origin were cultured as monolayers and exposed to CV-6209, an alkyl-phospholipid analog and antagonist of platelet activating factor. This drug had very potent antiproliferative effects on the studied human glioma cell lines; IC50 was 0.9 microM after 48 h treatment and 0.2 microM after 2 weeks treatment. At these doses no growth inhibitory effect was noted on the normal glia cells. The effects on the glioma cells were reversible in the dose intervals, where cell proliferation, 3H-thymidine and 14C-methionine uptakes were greatly inhibited. The simultaneous administration of platelet activating factor [(R)PAF] did not influence the antiproliferative effects of CV-6209 on the cells cultured as monolayers. The structurally similar analog CV-3988 also had antiproliferative effects, although at 10 times higher concentration than CV-6209. Two other, structurally unrelated, PAF-antagonists (WEB-2086 and TCV-309) gave effects only at very high concentrations. The U-343 MGa cell line was also exposed to CV-6209 when growing as multicellular spheroids. The studies on the spheroid cultures also demonstrated good antitumoral effects with decreases of both the volume growth and the thymidine uptake. The simultaneous administration of (R)PAF reversed the inhibitory effect of CV-6209 on thymidine incorporation. This study demonstrates a strong antitumoral effect at low concentrations of CV-6209. The antiproliferative effects were probably primarily related to the ether-lipid structure and not to the PAF-antagonistic properties. The good antitumoral effect of CV-6209 on both monolayer and spheroid cultures and the possible PAF-antagonistic properties are discussed. |
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Authors:
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I Gáti; M Bergström; C Muhr; J Carlsson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Prostaglandins, leukotrienes, and essential fatty acids Volume: 43 ISSN: 0952-3278 ISO Abbreviation: Prostaglandins Leukot. Essent. Fatty Acids Publication Date: 1991 Jun |
Date Detail:
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Created Date: 1991-10-10 Completed Date: 1991-10-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8802730 Medline TA: Prostaglandins Leukot Essent Fatty Acids Country: SCOTLAND |
Other Details:
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Languages: eng Pagination: 103-10 Citation Subset: IM |
Affiliation:
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Department of Neurology, Akademiska Hospital, Uppsala University, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Division
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drug effects* Cell Line Cell Survival / drug effects DNA Replication / drug effects Glioma Humans Kinetics Methionine / metabolism Neuroglia Platelet Activating Factor / antagonists & inhibitors* Pyridinium Compounds / pharmacology* Thymidine / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Platelet Activating Factor; 0/Pyridinium Compounds; 100488-87-7/CV 6209; 50-89-5/Thymidine; 63-68-3/Methionine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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