Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six new cell lines have been established from human neuroblastomas. Cell line SMS-KAN, from primary tumor before therapy, and line SMS-KANR, from bone marrow after chemotherapy and radiotherapy, were established from the same patient. Cell lines SMS-KCN (from primary tumor before any therapy) and SMS-KCNR (from bone marrow after chemotherapy) were established from another patient. Two other lines (SMS-MSN and SMS-SAN) were established from different patients before any therapy was given. Cell lines established from recurrent disease after chemotherapy (SMS-KANR and SMS-KCNR) had significantly shorter doubling times and increased plating efficiencies compared to those of cell lines derived from the same patient before chemotherapy (SMS-KAN and SMS-KCN). All cell lines contained tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine-beta-hydroxylase. Measurable amounts of choline acetyltransferase were also detected in SMS-KAN and SMS-KANR. Karyotype analysis showed all cell lines except SMS-MSN to be pseudodiploid with modal numbers of 46 and deletions of the short arm of chromosome 1; SMS-MSN had a modal number of 57-58 chromosomes. All cell lines had double-minute chromosomes, except SMS-KANR, which had abnormally banding regions. These new cell lines provide in vitro models of neuroblastoma suitable for the study of differences in neuroblastoma cell populations before chemotherapy as compared to the cell populations that proliferate after therapy.
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PMID:Characterization of human neuroblastoma cell lines established before and after therapy. 345 56

Our laboratory has synthesized two new phenolic thioether amines, N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) and N[2-[(4-propionyloxyphenyl)thio]ethyl] propionamide (N,O-diPr-4-S-CAP). These compounds, along with the previously described phenolic thioether amine N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) and its acetyl form (N,O-diAc-4-S-CAP), are tyrosine-amine derivative analogues. The cytotoxicity of these compounds is thought to be tyrosinase dependent, which may make them suitable for targeted anti-melanoma therapy since only melanocytes and their malignant counterparts contain this active enzyme. To further investigate this hypothesis, we performed MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assays to determine the cytotoxicity of these compounds in 10 different cell lines. Specifically, we examined to what extent cytotoxicity is related to tyrosinase and tyrosine hydroxylase activity using melanoma and neuroblastoma cells, which have a common metabolic pathway using tyrosinase and tyrosine hydroxylase, respectively. The most sensitive cell line was the highly pigmented SK-MEL-23 melanoma cell line, which shows a very high tyrosinase activity with the highest melanin pigmentation. KAN and SK-NSH (two neuroblastoma cell lines), which have no tyrosinase activity but high tyrosine hydroxylase, were also sensitive. However, C32 (a non-pigmented melanoma with a lower tyrosinase activity) was also sensitive, and MeWo (a moderately pigmented melanoma with a high tyrosinase activity) was less sensitive. This in vitro study may indicate that there is a non-tyrosinase-mediated mechanism of cytotoxicity for phenolic thioether amines in addition to the tyrosinase-mediated one described previously.
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PMID:Comparison of in vitro cytotoxicity of N-acetyl and N-propionyl derivatives of phenolic thioether amines in melanoma and neuroblastoma cells and the relationship to tyrosinase and tyrosine hydroxylase enzyme activity. 1071 35