TY - JOUR
T1 - Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans
AU - Yun, Dae Gyu
AU - Lee, Dong Gun
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Candida albicans is a common yeast that resides in the human body, but can occasionally cause systemic fungal infection, namely candidiasis. As this infection rate is gradually increasing, it is becoming a major problem to public health. Accordingly, we for the first time investigated the antifungal activity and mode of action of silibinin, a natural product extracted from Silybum marianum (milk thistle), against C. albicans. On treatment with 100 μM silibinin, generation of reactive oxygen species (ROS) from mitochondria, which can cause yeast apoptosis via oxidative stress, was increased by 24.17% compared to that in untreated cells. Subsequently, we found disturbances in ion homeostasis such as release of intracellular K+ and accumulation of cytoplasmic and mitochondrial Ca2+. Among these phenomena, mitochondrial Ca2+ overload particularly plays a crucial role in the process of apoptosis, promoting the activation of pro-apoptotic factors. Therefore, we investigated the significance of mitochondrial Ca2+ in apoptosis by employing 20 mM ruthenium red (RR). Additional apoptosis hallmarks such as mitochondrial membrane depolarization, cytochrome c release, caspase activation, phosphatidylserine (PS) exposure, and DNA damage were observed in response to silibinin treatment, whereas RR pre-treatment seemed to block these responses. In summary, our results suggest that silibinin induces yeast apoptosis mediated by mitochondrial Ca2+ signaling in C. albicans.
AB - Candida albicans is a common yeast that resides in the human body, but can occasionally cause systemic fungal infection, namely candidiasis. As this infection rate is gradually increasing, it is becoming a major problem to public health. Accordingly, we for the first time investigated the antifungal activity and mode of action of silibinin, a natural product extracted from Silybum marianum (milk thistle), against C. albicans. On treatment with 100 μM silibinin, generation of reactive oxygen species (ROS) from mitochondria, which can cause yeast apoptosis via oxidative stress, was increased by 24.17% compared to that in untreated cells. Subsequently, we found disturbances in ion homeostasis such as release of intracellular K+ and accumulation of cytoplasmic and mitochondrial Ca2+. Among these phenomena, mitochondrial Ca2+ overload particularly plays a crucial role in the process of apoptosis, promoting the activation of pro-apoptotic factors. Therefore, we investigated the significance of mitochondrial Ca2+ in apoptosis by employing 20 mM ruthenium red (RR). Additional apoptosis hallmarks such as mitochondrial membrane depolarization, cytochrome c release, caspase activation, phosphatidylserine (PS) exposure, and DNA damage were observed in response to silibinin treatment, whereas RR pre-treatment seemed to block these responses. In summary, our results suggest that silibinin induces yeast apoptosis mediated by mitochondrial Ca2+ signaling in C. albicans.
KW - Ca
KW - Candida a lbicans
KW - Silibinin
KW - Yeast apoptosis
UR - http://www.scopus.com/inward/record.url?scp=84987974689&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2016.09.008
DO - 10.1016/j.biocel.2016.09.008
M3 - Article
C2 - 27639679
AN - SCOPUS:84987974689
SN - 1357-2725
VL - 80
SP - 1
EP - 9
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -