title: Sirtuin 1 (SIRT1) Deacetylase Activity and NAD⁺/NADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death.
abstract: Capsaicin is considered a chemopreventive agent by virtue of its selective antigrowth activity, commonly associated with apoptosis, against cancer cells. However, noncancerous cells possess relatively higher tolerance to capsaicin, although the underlying mechanism for this difference remains unclear. Hence, this study aimed to elucidate the differential effects of capsaicin on cell lines from lung tissues by addressing the signal pathway leading to two types of cell death. In MRC-5 human fetal lung cells, capsaicin augmented silent mating type information regulation 1 (SIRT1) deacetylase activity and the intracellular NAD(+)/NADH ratio, decreasing acetylation of p53 and inducing autophagy. In contrast, capsaicin decreased the intracellular NAD(+)/NADH ratio, possibly through inhibition of tumor-associated NADH oxidase (tNOX), and diminished SIRT1 expression leading to enhanced p53 acetylation and apoptosis. Moreover, SIRT1 depletion by RNA interference attenuated capsaicin-induced apoptosis in A549 cancer cells and autophagy in MRC-5 cells, suggesting a vital role for SIRT1 in capsaicin-mediated cell death. Collectively, these data not only explain the differential cytotoxicity of capsaicin but shed light on the distinct cellular responses to capsaicin in cancerous and noncancerous cell lines.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.
authors.forename: Huei-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.
authors.forename: Lilly J
authors.initials: LJ
authors.lastname: Su
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.|Graduate Institute of Basic Medicine, China Medical University , Taichung 40402, Taiwan.|Department of Medical Research, China Medical University Hospital , Taichung 40402, Taiwan.|Department of Biotechnology, Asia University , Taichung 41354, Taiwan.
authors.forename: Pin Ju
authors.initials: PJ
authors.lastname: Chueh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology; D009243:NAD / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D009243:NAD; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D002211:Capsaicin
keywords: apoptosis; autophagy; capsaicin; silent mating type information regulation 1 (sirtuin 1, SIRT1); tumor-associated NADH oxidase (tNOX, ENOX2)