cellular apoptosis: an alternative mechanism of action for caspofungin against candida glabrata

Background and purpose: although the mechanism of action for echinocandins is known, the physiological mechanisms by which these antifungal agents cause cell death via the classical apoptotic pathways are not well-defined yet. regarding this, the present study aimed to evaluate the mechanisms of caspofungin-induced candida glabrata cell death. materials and methods: for the purpose of the study, the minimum inhibitory concentration (mic) of caspofungin against c. glabrata (atcc 90030) was determined using the broth microdilution reference method (clsi m27-a2 and m27-s4). the annexin v and propidium iodide staining was performed to determine the way through which caspofungin acts against c. glabrata (i.e., through the induction of apoptosis and/or necrosis). additionally, the possible effect of caspofungin on inducing the expression of two apoptotic genes, namely mca1 and nuc, was studied using the real-time polymerase chain reaction assay. results: according to the obtained mic value (0.5 μg/ml), c. glabrata, exposed to 0.25, 0.5, and 1 μg/ml of caspofungin, exhibited the features of late apoptosis/necrosis after 18 h of incubation. furthermore, the use of 0.25, 0.5, and 1 μg/ml caspofungin induced apoptosis (early/late) in 14.67%, 17.04%, and 15.89% of the cells, respectively. the results showed a significant difference between the percentages of early-apoptotic cells at the three concentrations (p<0.05). in addition, the rate of necrosis was significantly greater than that of apoptosis in response to caspofungin. accordingly, necrosis occurred in 71.26%, 71.26%, and 61.26% of the cells at the caspofungin concentrations of 0.25, 0.5, and 1 μg/ml, respectively (p<0.05). the analysis of the data in the rest software demonstrated a significant increase in the expression of mca1 and nuc1 genes (p<0.05). conclusion: as the findings of the present study indicated, caspofungin promoted both necrosis and apoptosis of c. glabrata cells at concentrations higher than or equal to the mic value.