Linked Life Data

1505078

Source:http://linkedlifedata.com/resource/pubmed/id/1505078

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-9-21
pubmed:abstractText
The rationale for melanoma-specific antitumor agents containing phenolic amines is based in part on the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. The phenolic amine compounds 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) inhibited in situ thymidylate synthase activity in pigmented melanoma cell lines but had little or no effect on nonpigmented and nonmelanoma cell lines. Theophylline, a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, increased tyrosinase activity and potentiated the inhibition of in situ thymidylate synthase by N-Ac-4-S-CAP. The inhibition of in situ thymidylate synthase by both drugs in pigmented melanoma cells correlated with the inhibition of DNA synthesis and cell growth and was not due to an indirect effect caused by inhibition of the enzyme dihydrofolate reductase. 4-S-CAP inhibition of thymidylate synthase activity in cell free extracts required oxidation of the drug. In the presence of tyrosinase, the concentration causing a 50% inhibition of thymidylate synthase activity (IC50) in cell-free extracts was less than 10 microM, but no inhibition was observed in its absence, even at a drug concentration of 500 microM. Two reducing agents, dithioerythritol and glutathione, effectively blocked the inhibition of thymidylate synthase by oxidized 4-S-CAP. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone-mediated mechanism of inhibition of DNA synthesis via inhibition of thymidylate synthase may be uniquely important in the expression of phenolic amine cytotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-S-cysteaminylphenol, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cysteamine, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Leucovorin, http://linkedlifedata.com/resource/pubmed/chemical/Monophenol Monooxygenase, http://linkedlifedata.com/resource/pubmed/chemical/N-acetyl-4-S-cysteaminylphenol, http://linkedlifedata.com/resource/pubmed/chemical/Phenols, http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts, http://linkedlifedata.com/resource/pubmed/chemical/Theophylline, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase, http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
394-400
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Thymidylate synthase as a target enzyme for the melanoma-specific toxicity of 4-S-cysteaminylphenol and N-acetyl-4-S-cysteaminylphenol.
pubmed:affiliation
Department of Radiation Oncology, University of Pittsburgh, PA 15213.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't