Abstract
Quinine, the widely used antimalaria agent, was found to increase the cytotoxicity of epideoxorubicin (epiDXR) in resistant DHD/K12 rat colon cancer cells in vitro. Quinine appeared as slightly less effective than quinidine or verapamil for anthracycline potentiation but its weaker cardiotoxicity could counterbalance this disadvantage in vivo. Serum from six patients treated by conventional doses of quinine (25-30 mg kg-1 day-1) was demonstrated to enhance the accumulation of epiDXR in DHD/K12 cells as judged by fluorescence microscopy and HPLC assay (1.6 to 6-fold compared with control serum). In this patients quinine concentrations in serum ranged from 4.4 to 10.1 micrograms ml-1. Our results suggest that quinine could be safely used as anthracycline resistance modifier in clinical practice.
Highlights
Primary or acquired resistance to anthracyclines of human cancers is partly associated with the overexpression of a membrane glycoprotein (P 170) that effluxes drugs out of cancer cells (Goldstein et al, 1989; Dalton et al, 1989)
Use of resistance modifiers in clinical practice is still a problem due to the toxicity of these agents that precludes the achievement of effective concentrations in patient serum (Gottesman & Pastan, 1989; Genne et al, 1990)
In this paper we report that quinine, the widely used antimalaria drug, enhanced in vitro the cytotoxicity of epidoxorubicin in resistant colon cancer cells
Summary
Primary or acquired resistance to anthracyclines of human cancers is partly associated with the overexpression of a membrane glycoprotein (P 170) that effluxes drugs out of cancer cells (Goldstein et al, 1989; Dalton et al, 1989). Anthracycline resistance may be altered in vitro by a variety of agents such as verapamil (Tsuruo et al, 1982), quinidine (Tsuruo et al, 1984), amiodarone (Chauffert et al, 1986) or cyclosporine (Slater et al, 1986). In this paper we report that quinine, the widely used antimalaria drug, enhanced in vitro the cytotoxicity of epidoxorubicin in resistant colon cancer cells. Serum of quinine treated patients was demonstrated to increase the cellular accumulation of the anthracycline in resistant cells
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