Document Detail

Effects of tyrosinase activity on the cytotoxicity of 3,4-dihydroxybenzylamine and buthionine sulfoximine in human melanoma cells.
MedLine Citation:
PMID:  2117268     Owner:  NLM     Status:  MEDLINE    
The rationale for melanoma specific dihydroxybenzene containing antitumor agents is based in part upon the ability of the enzyme tyrosinase to oxidize these pro drugs to toxic intermediates. In situ tyrosinase activity was demonstrated to be affected by both cell density and time from plating in pigmented melanoma cells. Phenylthiourea, which completely inhibited tyrosinase activity with minimal cytotoxicity was found to block the growth inhibitory activity of the antitumor dopamine analog 3,4-dihydroxybenzylamine (3,4-DHBA) (NSC 263475). The antioxidant dithioerythritol was also found to inhibit tyrosinase activity and to block the growth inhibitory effects of 3,4-DHBA in pigmented melanoma cell lines. Buthionine sulfoximine (BSO) was shown to be cytotoxic to melanoma cells and its growth inhibitory effects appears to correlate with tyrosinase levels. Furthermore, BSO was shown to potentiate the growth inhibitory effects of 3,4-DHBA on marginally pigmented human melanoma cell lines.
J A Prezioso; G B Fitzgerald; M M Wick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society     Volume:  3     ISSN:  0893-5785     ISO Abbreviation:  Pigment Cell Res.     Publication Date:    1990 Mar-Apr
Date Detail:
Created Date:  1990-09-18     Completed Date:  1990-09-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8800247     Medline TA:  Pigment Cell Res     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  49-54     Citation Subset:  IM    
Division of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
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MeSH Terms
Antimetabolites / metabolism,  toxicity*
Buthionine Sulfoximine
Catechol Oxidase / metabolism*
Cell Count
Dithioerythritol / pharmacology
Dopamine / analogs & derivatives*,  metabolism,  toxicity
Glutathione / metabolism
Melanoma / metabolism,  pathology*
Methionine Sulfoximine / analogs & derivatives*,  metabolism,  toxicity
Monophenol Monooxygenase / metabolism*,  pharmacology
Phenylthiourea / pharmacology
Time Factors
Tumor Cells, Cultured / drug effects,  metabolism,  pathology
Grant Support
Reg. No./Substance:
0/Antimetabolites; 103-85-5/Phenylthiourea; 1982-67-8/Methionine Sulfoximine; 37491-68-2/3,4-dihydroxybenzylamine; 5072-26-4/Buthionine Sulfoximine; 6892-68-8/Dithioerythritol; 70-18-8/Glutathione; EC Oxidase; EC Monooxygenase

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

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