Effect of tamoxifen on mitoxantrone cytotoxicity in drug-sensitive and multidrug-resistant MCF-7 cells. 1995

P B Desai, and R Bhardwaj, and B Damle
Division of Medicinal Chemistry and Pharmaceutics, School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470, USA.

The influence of the antiestrogen tamoxifen (TAM) on the activity of mitoxantrone (MXN), was evaluated against wild-type MCF-7/WT and their multidrug-resistant variant MCF-7/ADR cells. Multidrug resistance (MDR) in this cell line which was selected for resistance to Adriamycin (ADR), is associated with increased expression of P-glycoprotein (P-gp). In a clonogenic assay it was observed that TAM (1-10 microM) significantly enhanced the activity of MXN in the MCF-7/ADR but not in the drug-sensitive cell line. Isobologram analysis indicated that the effect of the combination was additive in the parental MCF-7/WT cells and strongly synergistic in the MDR MCF-7/ADR cells. Also, TAM (10 microM) caused a three-fold increase in the steady-state levels (Css) of MXN in MCF-7/ADR cells but did not modulate MXN levels in MCF-7/WT cells. The observed synergism in MCF-7/ADR cells was perhaps due to the increase in Css of MXN that may involve interaction of TAM with P-gp. The combination of MXN and TAM may be useful in the treatment of drug-sensitive and drug-resistant breast cancer.

UI MeSH Term Description Entries
D008942 Mitoxantrone An anthracenedione-derived antineoplastic agent. Mitozantrone,CL-232325,DHAQ,Mitoxantrone Acetate,Mitoxantrone Hydrochloride,Mitroxone,NSC-279836,NSC-287836,NSC-299195,NSC-301739,NSC-301739D,Novantron,Novantrone,Onkotrone,Pralifan,Ralenova,Acetate, Mitoxantrone,CL 232325,CL232325,Hydrochloride, Mitoxantrone,NSC 279836,NSC 287836,NSC 299195,NSC 301739,NSC 301739D,NSC279836,NSC287836,NSC299195,NSC301739,NSC301739D
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013629 Tamoxifen One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM. ICI-46,474,ICI-46474,ICI-47699,Nolvadex,Novaldex,Soltamox,Tamoxifen Citrate,Tomaxithen,Zitazonium,Citrate, Tamoxifen,ICI 46,474,ICI 46474,ICI 47699,ICI46,474,ICI46474,ICI47699
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014410 Tumor Stem Cell Assay A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents. Clonogenic Cell Assay, Tumor,Colony-Forming Units Assay, Tumor,Neoplasm Stem Cell Assay,Stem Cell Assay, Tumor,Colony Forming Units Assay, Tumor
D018432 Drug Resistance, Multiple Simultaneous resistance to several structurally and functionally distinct drugs. Drug Resistance, Extensively,Extensively Drug Resistance,Extensively-Drug Resistance,Multidrug Resistance,Multi-Drug Resistance,Extensively Drug Resistances,Extensively-Drug Resistances,Multiple Drug Resistance,Resistance, Extensively Drug,Resistance, Extensively-Drug,Resistance, Multiple Drug

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