Dill (Anethum graveolens L.) seed essential oil induces Candida albicans apoptosis in a metacaspase-dependent manner Yuxin CHEN a,1 , Hong ZENG a,b,1 , Jun TIAN a , Xiaoquan BAN a , Bingxin MA a , Youwei WANG a, * a Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), Institute of TCM and Natural Products, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, PR China b Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim University, Alar 843300, Xinjiang, PR China article info Article history: Received 3 October 2013 Received in revised form 16 February 2014 Accepted 18 February 2014 Available online 12 March 2014 Corresponding Editor: Mark Ramsdale Keywords: ATPase activity Cyt C release L-cysteine Staining Ultrastructure abstract Dill (Anethum graveolens L.) has been used in traditional Uighur medicine for its various pharmacological activities. Previous studies have suggested that dill seed essential oil (DSEO) has anti-Candida potential and the mechanism of its action also has been studied. Our study examined whether DSEO induces apoptosis in the human pathogen Candida al- bicans ATCC 64550. Our results indicate that C. albicans ATCC 64550 cells treated with DSEO show some typical apoptosis characters, such as decrease in adenosine triphosphatase (ATPase) activity, chromatin condensation, nuclear fragmentation, and phosphatidylserine (PS) exposure. The DSEO promoted cytochrome c (cyt c) release and metacaspase activa- tion, which resulted in C. albicans ATCC 64550 apoptosis. L-cysteine prevented the DSEO- induced nuclear fragmentation, PS externalization, and metacaspase activation, thus indi- cating that the reactive oxygen species (ROS) is an important mediator of DSEO-induced apoptosis. To our knowledge, this study is the first to report the induction of apoptosis of this pathogen with concomitant metacaspase activation by DSEO. ª 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved. Introduction Candida species, such as Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, cause serious fungal in- fections that lead to candidiasis. Within the genera Candida, C. albicans is the most virulent species and the predominant spe- cies found on oral mucosal layers, in vaginal infections, and in invasive bloodstream infections, which was reviewed by Pereira Gonzales & Maisch (2012). Recently, Maschmeyer (2006) reviewed that the morbidity and mortality of candidia- sis increased dramatically because of the growing number of immunocompromised patients. The antibiotics used in clinics affect specific fungal cellular targets reviewed by Odds et al. (2003), such as ergosterol, DNA, RNA, and protein syntheses, as well as microtubule assembly. However, some of these drugs are associated with high human toxicity, high cost, and drugedrug interactions. The number of resistant strains is increasing along with the long-term and large-scale * Corresponding author. Tel.: þ86 (0) 27 68759323; fax: þ86 (0) 27 68759010. E-mail addresses: wyw@whu.edu.cn, wyw@wbgcas.cn (Y. Wang). 1 These authors contributed equally to the work. journal homepage: www.elsevier.com/locate/funbio fungal biology 118 (2014) 394 e401 1878-6146/$ e see front matter ª 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.funbio.2014.02.004