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PMID: 7685615 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Differential modulation of doxorubicin toxicity to multidrug and intrinsically drug resistant cell lines by anti-oestrogens and their major metabolites.

British journal of cancer ·Vol. 67 ·No. 6 ·1993-06-00 ·Pages 1189-95

Kirk J, Houlbrook S, Stuart NS, Stratford IJ, Harris AL, Carmichael J

Abstract

The ability of the anti-oestrogens tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites to modify doxorubicin (dox) toxicity to intrinsically resistant and multidrug resistant cell lines was compared, using human breast and lung cancer, and Chinese hamster ovary cell lines. The anti-oestrogens significantly enhanced dox toxicity to multidrug resistant, P-glycoprotein-positive cell lines, but did not affect toxicity to intrinsically resistant, P-glycoprotein-negative cells. Modification was observed at clinically achievable anti-oestrogen concentrations. Toremifene and tamoxifen would therefore appear to be good candidates for in vivo studies as MDR modulating agents in selected patients with P-glycoprotein-positive tumours.

Related Genes
MDR
MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1 Animals Antibodies, Monoclonal Breast Neoplasms/drug therapy,pathology CHO Cells Carrier Proteins/analysis,immunology Cell Division/drug effects Cricetinae Doxorubicin/toxicity Drug Interactions Drug Resistance Drug Screening Assays, Antitumor Epitopes/analysis Estrogen Antagonists/metabolism,pharmacology Humans Lung Neoplasms/drug therapy,pathology Membrane Glycoproteins/analysis,immunology Tamoxifen/analogs & derivatives,metabolism,pharmacology Toremifene/metabolism,pharmacology Tumor Cells, Cultured/drug effects
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 Antibodies, Monoclonal Carrier Proteins Epitopes Estrogen Antagonists Membrane Glycoproteins Tamoxifen afimoxifene Toremifene Doxorubicin N-desmethyltamoxifen 4-hydroxytoremifene
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kirk J
ICRF Laboratory, John Radcliffe Hospital, Headington, Oxford, UK.
Houlbrook S
Stuart N S
Stratford I J
Harris A L
Carmichael J
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/bjc.1993.224
Published
1993-06-00
Pages
1189-95
Language
English
Region
England
NLM ID
0370635
PMCID
PMC1968530
Subset
IM
Grants
Medical Research Council · G0500366 · United Kingdom
External Links
PubMed source DOI: 10.1038/bjc.1993.224 PMC Full Text View journal details
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