Silibinin triggers yeast apoptosis related to mitochondrial Ca²⁺ influx in Candida albicans

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• 作者：Dae Gyu Yun ; Dong Gun Lee ; ^{dglee222@knu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MIC ; minimum inhibitory concentration ; YPD ; yeast extract peptone dextrose ; YM ; yeast mold ; ROS ; reactive oxygen species ; PBS ; phosphate buffered saline ; H2DCFDA ; 2&prime ; 7&prime ; -dichlorodihydrofluorescein diacetate ; RR ; ruthenium red ; PI ; propidium iodide ; PPB ; potassium phosphate buffer ; TUNEL ; terminal deoxynucleotidyl transferase dUTP nick end labeling ; Δψm ; mitochondrial membrane potential ; PS ; phosphatidylserine ; ER ; endoplasmic reticulum
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：80
• 期：Complete
• 页码：1-9
• 全文大小：2146 K

文摘

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.