Potential usefulness of quinine to circumvent the anthracycline resistance in clinical practice.
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.
Research Group on Digestive Cancers, INSERM U.252, Dijon, France.
B
B
Chauffert
H
H
Pelletier
C
C
Corda
E
E
Solary
L
L
Bedenne
D
D
Caillot
F
F
Martin
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance; D004357:Drug Synergism; D015251:Epirubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D011803:Quinine; D014700:Verapamil; D011802:Quinidine