| Toxicity of phorbol esters for human epithelial cells expressing a mutant ras oncogene. | |
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MedLine Citation:
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PMID: 8280376 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phorbol esters and related compounds provide a promising source of potential anticancer agents. The mechanism of their toxicity, however, is unclear, and interpretation has been complicated by the conflicting responses exhibited by different transformed cell lines. Previously we showed that in primary thyroid follicular cells, expression of mutant p21ras conferred a striking sensitivity to the toxic effects of phorbol esters. We have now extended this work using a thyroid cell line with an inducible mutant ras gene to exclude the possibility that this result was a trivial consequence of the marked growth stimulation induced in these cells by mutant p21ras. Furthermore, by assessing the action of a panel of phorbol esters and a potential chemotherapeutic agent, bryostatin, we demonstrated that this phenomenon was only a function of biologically active phorbol esters. These results provide a molecular rationale for the development of phorbol ester analogues as chemotherapeutic agents. |
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Authors:
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T Dawson; J Bond; N Eccles; D Wynford-Thomas |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Molecular carcinogenesis Volume: 8 ISSN: 0899-1987 ISO Abbreviation: Mol. Carcinog. Publication Date: 1993 |
Date Detail:
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Created Date: 1994-02-17 Completed Date: 1994-02-17 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 280-9 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Bryostatins Cell Division / drug effects Cell Line DNA / drug effects, genetics Epithelial Cells Epithelium / drug effects, physiology Gene Expression Regulation / drug effects*, genetics Genes, ras / genetics* Humans Lactones / toxicity Macrolides Models, Biological Mutation / genetics* Phorbol 12,13-Dibutyrate / toxicity Phorbol Esters / toxicity* Proto-Oncogene Proteins p21(ras) / genetics, physiology Structure-Activity Relationship Tetradecanoylphorbol Acetate / toxicity Thyroid Gland / cytology, drug effects*, physiology* Zinc / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Bryostatins; 0/Lactones; 0/Macrolides; 0/Phorbol Esters; 16561-29-8/Tetradecanoylphorbol Acetate; 24928-17-4/phorbol-12,13-didecanoate; 37558-16-0/Phorbol 12,13-Dibutyrate; 7440-66-6/Zinc; 83314-01-6/bryostatin 1; 9007-49-2/DNA; EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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