title: Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways.
abstract: Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa. In this study, several experiments were performed to investigate the effects of CAP on BCa cells (5637 and T24) and NOD/SCID mice. Our results showed that CAP could suppress BCa tumorigenesis by inhibiting its proliferation both in vitro and in vivo. Moreover, CAP induced cell cycle arrest at G0/G1 phase and ROS production. Importantly, our studies revealed a strong increase of FOXO3a after treatment with CAP. Furthermore, we observed no significant alteration of apoptosis by CAP, whereas Catalase and SOD2 were considerably upregulated, which could clear ROS and protect against cell death. Thus, our results suggested that CAP could inhibit viability and tumorigenesis of BCa possibly via FOXO3a-mediated pathways.
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. qky1009@whu.edu.cn.|Department of Urology, The Fifth Hospital of Wuhan, Wuhan 430050, China. qky1009@whu.edu.cn.
authors: Kaiyu
authors: K
authors: Qian
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. gangwang.uro@whu.edu.cn.
authors: Gang
authors: G
authors: Wang
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. caorui@whu.edu.cn.
authors: Rui
authors: R
authors: Cao
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. liutaozaiwuda@whu.edu.cn.|Department of Urology, Jingzhou Central Hospital, Jingzhou 434020, China. liutaozaiwuda@whu.edu.cn.
authors: Tao
authors: T
authors: Liu
authors: Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China. qgf0220@zju.edu.cn.
authors: Guofeng
authors: G
authors: Qian
authors: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. xyguan@hku.hk.
authors: Xinyuan
authors: X
authors: Guan
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. guozqmail@sina.com.
authors: Zhongqiang
authors: Z
authors: Guo
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. yu.xiao@whu.edu.cn.|Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. yu.xiao@whu.edu.cn.
authors: Yu
authors: Y
authors: Xiao
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. wangxinghuan@whu.edu.cn.
authors: Xinghuan
authors: X
authors: Wang
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099156:Superoxide Dismutase 2
chemical_list: D002211:Capsaicin; D002374:Catalase; D000071316:Forkhead Box Protein O3; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C499517:FOXO3 protein, human
keywords: ROS; bladder cancer; capsaicin; cell cycle; migration; xenograft