The riminophenazine agents clofazimine and B669 reverse acquired multidrug resistance in a human lung cancer cell line.

Abstract

The potential of the riminophenazine agents clofazimine and B669, at therapeutically relevant concentrations, to reverse P-glycoprotein-mediated multidrug-resistance (MDR) in a human lung cancer cell line (H69/LX4) has been investigated in vitro. Cyclosporin A, a well-documented MDR-modifying agent, was included for comparison. Clofazimine, B669 and cyclosporin A at minimally cytotoxic concentrations of 1, 0.5 and 5 micrograms/ml, respectively, were equally effective in restoring sensitivity to vinblastine, doxorubicin, daunorubicin and mitomycin C in the H69/LX4 cell line. All three chemosensitizing agents also increased the accumulation of [14C]vinblastine by H69/LX4 cells. Riminophenazines, which are relatively non-toxic, non-carcinogenic and non-myelosuppressive agents, are promising contenders for evaluation in experimental and clinical oncology as modulators of acquired MDR.

• Authors: C E Van Rensburg, R Anderson, M S Myer, G K Jooné, J F O'Sullivan
• Journal: Cancer letters (Cancer Lett) Vol. 85 Issue 1 Pg. 59-63 (Sep 30 1994) ISSN: 0304-3835 [Print] Ireland
• PMID: 7923103 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Antineoplastic Agents
• Carbon Radioisotopes
• Vinblastine
• B 669
• Cyclosporine
• Clofazimine

Topics

• Anti-Infective Agents (pharmacology)
• Antineoplastic Agents (pharmacokinetics, pharmacology)
• Carbon Radioisotopes
• Carcinoma, Small Cell (drug therapy, metabolism)
• Cell Division (drug effects)
• Clofazimine (analogs & derivatives, pharmacology)
• Cyclosporine (pharmacology)
• Drug Interactions
• Drug Resistance, Multiple
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• Tumor Cells, Cultured
• Vinblastine (pharmacokinetics, pharmacology)