| Potency, selectivity and cell cycle dependence of catechols in human tumour cells in vitro. | |
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MedLine Citation:
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PMID: 3132176 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enhancement of the potency and melanoma-selectivity of redox agents was sought by two different approaches. In screening a series of catechols, derivatives of moderate half-life (dopa, dopamine, noradrenaline, 3,4-dihydroxybenzylamine, 3,4-dihydroxyphenylacetic acid; t1/2 12-33 hr) had significant toxicity (D37 20-30 microM) and selectivity for melanoma cells compared with HeLa. Less stable catechols (5-hydroxy- and 6-hydroxydopamine; t1/2 4 and 5 hr respectively) were toxic but lacked selectivity whereas more stable derivatives (4-hydroxyanisole, 2,3-dihydroxybenzoic acid; t1/2 greater than 72 hr) were less potent (D37 greater than 100 microM) and had poor selectivity. Gossypol, a complex catechol derivative, exhibited significant toxicity (D37 7.7 microM) but little selectivity. Enzymes capable of reacting with components of the culture medium and known to continuously generate hydrogen peroxide (glucose-6-oxidase) or superoxide ion (xanthine oxidase) exhibited a similar degree of selectivity as dopa, indicating that active oxygen species are more important mediators of catechol toxicity than quinones. Rhodamine 123, a cationic dye preferentially taken up by some tumour cells, was accumulated equally by melanoma and HeLa yet had a similar selectivity to that of dopa. In the second approach, the potency of dopa was found to be greatly enhanced during early S phase. This phenomenon, found with cells synchronised both by mitotic shake off and by 24 hr accumulation in G1S in the presence of 5 mM hydroxyurea, occurred during a period in which the proportion of cells in S phase cells was low. These results indicate that human cells are extremely sensitive to extracellular active oxygen species during a relatively short period in early S phase, and selective killing of asynchronous melanoma cells therefore requires agents capable of sustaining a redox effect for at least one cell cycle. |
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Authors:
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E P Kable; P G Parsons |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 37 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1988 May |
Date Detail:
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Created Date: 1988-06-30 Completed Date: 1988-06-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1711-5 Citation Subset: IM |
Affiliation:
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Queensland Institute of Medical Research, Herston, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Catechols
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toxicity* Cell Cycle* Cell Line Cell Survival / drug effects Dihydroxyphenylalanine / toxicity Dose-Response Relationship, Drug Glucose Oxidase / toxicity Humans Oxidation-Reduction Rhodamines / toxicity |
| Chemical | |
Reg. No./Substance:
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0/Catechols; 0/Rhodamines; 63-84-3/Dihydroxyphenylalanine; EC 1.1.3.4/Glucose Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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