title: Silibinin triggers yeast apoptosis related to mitochondrial Ca2+influx in Candida albicans.
abstract: 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 100μM 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 20mM 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.
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu, 41566, Republic of Korea.
authors.forename: Dae Gyu
authors.initials: DG
authors.lastname: Yun
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu, 41566, Republic of Korea. Electronic address: dglee222@knu.ac.kr.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004249:DNA Damage; D006706:Homeostasis / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020944:Silybum marianum / Q000737:chemistry; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D012838:Silymarin; D000077385:Silybin; D011188:Potassium; D002118:Calcium
keywords: Ca(2+); Candida a lbicans; Silibinin; Yeast apoptosis