Molecular mechanisms underlying the tetrandrine-mediated reversal of the fluconazole resistance of Candida albicans. (June 2013)

• Record Type: Journal Article
• Authors: Zhang, Xiaoli; Guo, Hui; Gao, Laiqiang; Song, Yanjun; Li, Shuixiu; Zhang, Hong
• Is Part Of: Pharmaceutical biology. Volume 51:Number 6(2013:Jun.)
• Page Start: 749
• Page End: 752
• Publication Date: 2013-06
• Subjects: Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.3109/13880209.2013.764537
• Languages: English
• ISSNs: 1388-0209

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context</italic>: Our previous study demonstrated that tetrandrine (TET) could reverse the resistance of <italic>Candida albicans</italic> to fluconazole.</p> <p> <italic>Objective</italic>: The aim of this study was to investigate the molecular mechanism underlying this action.</p> <p> <italic>Materials and methods</italic>: Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was performed to compare the expression levels of the drug resistance genes <italic>CDR1, CDR2, MDR1, FLU1</italic> and <italic>ERG11</italic> in fluconazole-sensitive CA-3 and resistant CA-16 cells that were either treated with FLC and/or TET or left as untreated controls. In addition, intracellular ATP levels were measured using an ATP assay kit, and the expression level of the energy metabolism gene <italic>ADH1</italic> was measured by real-time RT-PCR.</p> <p> <italic>Results</italic>: Compared with FLC/TET-free conditions, FLC + TET treatment strains showed statistically different (<italic>p</italic> < 0.05) expression of <italic>CDR1</italic> and <italic>CDR2</italic> (increased in the FLC-sensitive strains, while decreased in the FLC-resistant strains), <italic>MDR1</italic> (increased in the FLC-resistant strains), <italic>FLU1</italic> and <italic>ERG11</italic> (increased in the FLC-sensitive strains), <italic>ADH1</italic> (decreased in both the FLC-sensitive and the FLC-resistant strains). And also, the FLC + TET treatment decreased the intracellular ATP levels in both the FLC-sensitive and the FLC-resistant strains (<italic>p</italic> < 0.05).</p> <p> <italic>Discussion and conclusion</italic>: These results suggest that changes in the expression levels of the drug resistance genes <italic>CDR1</italic> and <italic>CDR2</italic>, the cellular ATP supply and the expression level of the energy metabolism gene <italic>ADH1</italic> contribute to the TET-mediated reversal of the fluconazole resistance of <italic>C. albicans</italic>.</p> </abstract>