Cecropin A-induced apoptosis is regulated by ion balance and glutathione antioxidant system in Candida albicans

Cecropin A, isolated from the giant silk moth Hyalophora cecropia, is a 37-mer peptide that exerts potent antimicrobial effects. We investigated cecropin A-induced apoptosis associated with ion balance and redox state of Candida albicans. The antifungal effect of cecropin A, associated with ion movement was verified by significant increase of cell viability following pretreatment of ion channel blockers. Cecropin A induced undesired ion movement such as calcium accumulation and potassium leakage. Furthermore, the reduction of phosphatidylserine (PS) externalization was detected following pretreatment of ion channel blockers. Based on these results, we confirmed that ion imbalance regulates the apoptotic activity of cecropin A. Moreover, cecropin A decreased NADPH and glutathione levels, which are crucial factors in the intracellular antioxidant defense system. The decreased intracellular antioxidant capacity induced oxidative stress by generating reactive oxygen species (ROS). Moreover, several apoptotic features such as mitochondrial depolarization, caspase activation, and DNA fragmentation were observed in cecropin A-treated cells. In conclusion, disrupted ion balance and intracellular glutathione redox state play a key role in cecropin A-induced apoptosis in C. albicans.