Circumvention of doxorubicin resistance in multi-drug resistant human leukaemia and lung cancer cells by the pure antioestrogen ICI 164384.

Abstract

ICI 164384, a new steroidal antioestrogen, entirely devoid of oestrogenic activity, modulates doxorubicin resistance in vitro. At non-cytotoxic concentrations, ICI 164384 potentiated the cytotoxicity of doxorubicin in a dose-dependent manner in both the classical multi-drug resistant (MDR) human leukaemia cell lines CEM/VLB 100 and CEM/VLB 1000 and the human small cell lung cancer cell line H69 LX4. ICI 164384 had no effect on the two respective parental cell lines, CEM/CCRF and H69 P. None of these cell lines expressed the oestrogen receptor. In comparative studies at concentrations ranging from 1.25 to 10 mumols/l, ICI 164384 was significantly more effective (1.2-6-fold) than tamoxifen in reducing the IC50 of doxorubicin in the CEM/VLB 100 line. In resistant cells, ICI 164384 increased 3H-daunomycin accumulation in a dose-dependent manner and was significantly more effective than tamoxifen at concentrations ranging from 2.5 to 10 mumol/l. ICI 164384 reduced the efflux of daunomycin from resistant cells more effectively than tamoxifen. These studies suggest that ICI 164384 is an effective modulator of MDR.

• Authors: X F Hu, G Nadalin, M De Luise, T J Martin, A Wakeling, R Huggins, J R Zalcberg
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 27 Issue 6 Pg. 773-7 ( 1991) ISSN: 0959-8049 [Print] England
• PMID: 1648945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Antagonists
• Polyunsaturated Alkamides
• Estradiol
• Doxorubicin
• ICI 164384
• Daunorubicin

Topics

• Carcinoma, Small Cell (pathology)
• Cell Division (drug effects)
• Cell Line
• Daunorubicin (metabolism)
• Doxorubicin (pharmacology)
• Drug Resistance
• Estradiol (analogs & derivatives, pharmacology)
• Estrogen Antagonists (pharmacology)
• Humans
• Leukemia, T-Cell (metabolism, pathology)
• Lung Neoplasms (pathology)
• Polyunsaturated Alkamides
• Tumor Cells, Cultured (drug effects)