An Insight on the Role of Nitric Oxide in Yeast Apoptosis of Curcumin-Treated Candida albicans

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An Insight on the Role of Nitric Oxide in Yeast Apoptosis of Curcumin‑Treated Candida albicans Min Seok Kwun1 · Dong Gun Lee1 Received: 18 February 2020 / Accepted: 14 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Nitric Oxide (NO) is a widely studied molecule due to its diverse biological functions. One of its activities, induction of apoptosis, is currently an area of active investigation in mammalian cells. However, there exists little information regarding the role of NO in yeast apoptosis. In an effort to investigate the mode of action by which NO induces programmed cell death in Candida albicans, we conducted a study on curcumin, a major bioactive compound, which is known as a potential apoptosis-inducing material due to several of its biological activities. First, NO generation was evaluated upon curcumin treatment. It is widely known that NO production is closely tied to cellular respiration, which is regulated by mitochondria. An increase in NO concentration leads to the inhibition of respiration and mitochondrial dysfunction. The hallmarks of mitochondrial dysfunction include a decrease in mitochondrial membrane potential along with increased mitochondrial mass, calcium concentration and ROS generation. A specific oxidative ROS compound, superoxide ( O−2  ), is strongly reactive with NO to form peroxynitrite ­(ONOO−). ­ONOO− disturbs intracellular redox levels, decreasing the overall ratio of glutathione (GSH). This leads to oxidative damage in C. albicans, triggering lethal DNA damage that eventually results in apoptosis. In the present study, a nitric oxide synthase (NOS) inhibitor, L-NG-Nitroarginine Methyl Ester (L-NAME), was used in each experiment. In all experiments, L-NAME pre-treatment of cells blocked the effects induced by curcumin, which indicates that nitric oxide is a component of the overall mechanism. In conclusion, NO account for an indispensable position in apoptosis of curcumin-treated C. albicans.

Introduction Curcumin is a polyphenol compound derived from the rhizome of Curcuma longa plants; it is the primary ingredient of turmeric and is widely used as an edible supplement in various countries [1]. Also known as diferuloylmethane (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene3,5-dione), curcumin is a beta-diketone, formed by methane groups in which two of the hydrogens are substituted with feruloyl groups [2]. Curcumin is currently renowned for its various beneficial effects in humans. These include its antiinflammatory, anti-proliferation and antioxidant activities [3]. Moreover, curcumin displays a wide range of antimicrobial properties [4]. Among these, its antifungal activity has been evaluated and explored by various studies [5]. These * Dong Gun Lee [email protected] 1



School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea

antifungal activities include a membrane-related mechanism against C. albicans [6] and minimum inhibitory detection against Paraco