Amiodarone inhibits multiple drug resistance in yeast Saccharomyces cerevisiae.
Amiodarone is a widely used antiarrhythmic drug. There is also evidence that amiodarone decreases multidrug resistance in human cell lines. In this paper, we have shown that amiodarone has similar effect on yeast, Saccharomyces cerevisiae, decreasing multiple drug resistance. Amiodarone stimulates the accumulation of ethidium bromide by inhibiting its efflux from the cells. The effect of amiodarone is much stronger on wild-type cells compared to the mutant with inactivated ABC-transporters. Interestingly, the action of amiodarone is additive with the one of chloroquine, a known inhibitor of ABC-transporters. We speculate that these findings could help in the development of antifungal drug mixes.
Knorre
Dmitry A
DA
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, GSP-2, Leninskie Gory, 119992, Moscow, Russia. knorre@belozersky.msu.ru
Krivonosova
Tatiana N
TN
Markova
Olga V
OV
Severin
Fedor F
FF
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000638:Amiodarone / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal / Q000187:drug effects*; D004996:Ethidium / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D029701:Saccharomyces cerevisiae Proteins; D004996:Ethidium; D000638:Amiodarone