Abstract
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.
Abbreviations
- ABC:
-
ATP-binding cassette
- MDR:
-
Multiple drug resitance
- EB:
-
Ethidium bromide
- C12-TPP:
-
Dodecyltriphenylphosphonium
References
Calich VL, Purchio A, Paula CR (1979) A new fluorescent viability test for fungi cells. Mycopathologia 66:175–177
Emerson LR, Skillman BC, Wolfger H, Kuchler K, Wirth DF (2004) The sensitivities of yeast strains deficient in PDR ABC transporters, to quinoline-ring antimalarial drugs. Ann Trop Med Parasitol 98:643–649
Foland TB, Dentler WL, Suprenant KA, Gupta ML Jr, Himes RH (2005) Paclitaxel-induced microtubule stabilization causes mitotic block and apoptotic-like cell death in a paclitaxel-sensitive strain of Saccharomyces cerevisiae. Yeast 22:971–978
Gupta SS, Ton VK, Beaudry V, Rulli S, Cunningham K, Rao R (2003) Antifungal activity of amiodarone is mediated by disruption of calcium homeostasis. J Biol Chem 278:28831–28839
Katzmann DJ et al (1995) Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae. Mol Cell Biol 15:6875–6883
Kolaczkowska A, Kolaczkowski M, Goffeau A, Moye-Rowley WS (2008) Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae. FEBS Lett 582:977–983
Leppert G, McDevitt R, Falco SC, Van Dyk TK, Ficke MB, Golin J (1990) Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces. Genetics 125:13–20
Lewis K (1994) Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem Sci 19:119–123
Maresova L, Muend S, Zhang YQ, Sychrova H, Rao R (2009) Membrane hyperpolarization drives cation influx and fungicidal activity of amiodarone. J Biol Chem 284:2795–2802
Muend S, Rao R (2008) Fungicidal activity of amiodarone is tightly coupled to calcium influx. FEMS Yeast Res 8:425–431
Pozniakovsky AI, Knorre DA, Markova OV, Hyman AA, Skulachev VP, Severin FF (2005) Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol 168:257–269
Raymond M, Ruetz S, Thomas DY, Gros P (1994) Functional expression of P-glycoprotein in Saccharomyces cerevisiae confers cellular resistance to the immunosuppressive and antifungal agent FK520. Mol Cell Biol 14:277–286
Sherman F (2002) Getting started with yeast. Methods Enzymol 350:3–41
van der Graaf WT et al (1991) In vitro and in vivo modulation of multi-drug resistance with amiodarone. Int J Cancer 48:616–622
van der Graaf WT et al (1994) Effects of amiodarone, cyclosporin A, and PSC 833 on the cytotoxicity of mitoxantrone, doxorubicin, and vincristine in non-P-glycoprotein human small cell lung cancer cell lines. Cancer Res 54:5368–5373
Varbiro G, Toth A, Tapodi A, Veres B, Sumegi B, Gallyas F Jr (2003) Concentration-dependent mitochondrial effect of amiodarone. Biochem Pharmacol 65:1115–1128
Wigler PW (1996) Cellular drug efflux and reversal therapy of cancer. J Bioenerg Biomembr 28:279–284
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by Axel Brakhage.
Rights and permissions
About this article
Cite this article
Knorre, D.A., Krivonosova, T.N., Markova, O.V. et al. Amiodarone inhibits multiple drug resistance in yeast Saccharomyces cerevisiae . Arch Microbiol 191, 675–679 (2009). https://doi.org/10.1007/s00203-009-0493-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00203-009-0493-8