Document Detail


Toxicity of phorbol esters for human epithelial cells expressing a mutant ras oncogene.
MedLine Citation:
PMID:  8280376     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T Dawson; J Bond; N Eccles; D Wynford-Thomas
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  8     ISSN:  0899-1987     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  1993  
Date Detail:
Created Date:  1994-02-17     Completed Date:  1994-02-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  280-9     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / 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:
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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