Capsaicin toxicity to the yeast Saccharomyces cerevisiae is not due to oxidative stress but to disruption of membrane structure

Capsaicin (8-methyl-N-vanillyl-6-nonenamide; CAP; Fig. 1A), a pungent ingredient in various red peppers of the genus Capsicum, is commonly used for its pungent taste as a frequent ingredient in the human diet. It is a pain-inducing agent [1] but has analgetic properties [2]. CAP has been reported to be cytocidal for different cancer cells in vitro [[3], [4], [5]], and to effectively inhibit tumor growth and induce apoptosis in vivo without toxic side effects. It has been proposed as a therapeutic agent for the treatment of leukemia [6]. CAP has also been suggested to have therapeutic potential for the treatment of gastric lesions [7], diabetic neuropathy [8], arthritis [9] as well as cardiac hyperexcitability [10]. CAP inhibits platelet aggregation [11]. This compound was reported to reduce adipose tissue and lower the level of triglycerides, stimulate carbohydrate oxidation, and decrease appetite [[12], [13]].

CAP can affect the redox status of various cells. It has antioxidant properties. CAP was demonstrated to be an •OH-inactivating ligand impeding the reduction in metal ions and inhibiting the production of •OH in Fenton-like reactions [14]. It was found to be a better antioxidant than ascorbic acid in the diphenylpicrylhydrazyl (DPPH) and 2,2′-azinobis [3-ethyl-2,3-dihydrobenzothiazole-6-sulphonate (ABTS) radical reduction tests and better antioxidant than butylhydroxytoluene (BHT) in the Ferric Reducing Antioxidant Power (FRAP) test, but worse than propyl gallate in the β-carotene bleaching test [15]. CAP scavenged galvinoxyl and peroxyl radicals [16], and inhibited lipid peroxidation, being more effective than α-tocopherol [17]. Nonetheless, CAP is also known to induce the generation of reactive oxygen species (ROS) in various cancer cell types [[18], [19], [20]]. CAP was reported to have considerable antimicrobial activity, i. a. Against the pathogenic bacteria Streptococcus pyogenes [21], the pathogenic yeast Candida albicans [22,23] and the yeast Saccharomyces cerevisiae [24], which may be important for food preservation.

The mechanism of CAP toxicity against microbial cells is not clear. There were reasons to suspect that it can involve oxidative stress like in the case of malignant cells. The aim of this study was to get an insight into this question using Saccharomyces cerevisiae as a model yeast species.

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