title: Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1).
abstract: Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. w101052018@gmail.com.|Tainan Municipal An-Nan Hospital, China Medical University, Tainan 70965, Taiwan. w101052018@gmail.com.
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. cornsugar@gmail.com.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. hikki4028@yahoo.com.tw.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. trista09081123@gmail.com.
authors.forename: Huei-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. s7213987@gmail.com.
authors.forename: Fong-Han
authors.initials: FH
authors.lastname: Jhuang
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. pjchueh@dragon.nchu.edu.tw.|Graduate Institute of Basic Medicine, China Medical University, Taichung 40402, Taiwan. pjchueh@dragon.nchu.edu.tw.|Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan. pjchueh@dragon.nchu.edu.tw.|Department of Biotechnology, Asia University, Taichung 41354, Taiwan. pjchueh@dragon.nchu.edu.tw.
authors.forename: Pin Ju
authors.initials: PJ
authors.lastname: Chueh
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase; D056564:Sirtuin 1; D002211:Capsaicin
keywords: ENOX2); apoptosis; cancer; capsaicin; silent mating type information regulation 1 (sirtuin1, SIRT1); tumor-associated NADH oxidase (tNOX