The Calcium Channel Blocker Verapamil Inhibits Oxidative Stress Response in Candida albicans

Candida albicans is a common opportunistic fungal pathogen, causing both superficial candidiasis and life-threatening systemic infections in immune-compromised individuals. Calcium signaling is responsible for this pathogen in responding to several stresses, such as antifungal drugs, alkaline pH and membrane-perturbing agents. Our recent study revealed that it is also involved in oxidative stress response. In this study, we investigated the effect of verapamil, an L-type voltage-gated calcium channel blocker, on oxidative stress response in this fungus. The addition of verapamil resulted in increased sensitivity to the oxidative agent H₂O₂, which is associated with a decrease of calcium fluctuation under the stress. Moreover, this agent caused enhanced oxidative stress, with increased levels of ROS and enhanced dysfunction of the mitochondria under the oxidative stress. Further investigations in SOD activity, GSH contents and expression of oxidative stress response-related genes indicated that the effect of verapamil is related to the repression of oxidative stress response. Our findings demonstrated that verapamil has an inhibitory effect on oxidative stress response, confirming the relationship between calcium signaling and oxidative stress in C. albicans. Therefore, calcium channels may be potential targets for therapy to enhance the efficacy of oxidative stress against C. albicans-related infections.