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In this study we describe the effects of tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P-glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected.

Original publication

DOI

10.1016/s0959-8049(05)80306-5

Type

Journal article

Journal

Eur J Cancer

Publication Date

1993

Volume

29A

Pages

1152 - 1157

Keywords

Amsacrine, Animals, Breast Neoplasms, CHO Cells, Cell Survival, Cisplatin, Cricetinae, Dose-Response Relationship, Drug, Drug Resistance, Humans, Lung Neoplasms, Melphalan, Tamoxifen, Toremifene, Tumor Cells, Cultured, Vinblastine