title: Capsaicin mediates caspases activation and induces apoptosis through P38 and JNK MAPK pathways in human renal carcinoma.
abstract: Renal cell carcinoma (RCC) is one of the tumors most refractory to chemotherapy to date. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin (CPS), a natural active ingredient of green and red peppers, and a ligand of transient receptor potential vanilloid type 1 (TRPV1), has been showed potential in suppression of tumorigenesis of several cancers. Nonetheless, the anti-cancer activity of CPS has never been studied in human RCC.
  
  
  
  CCK8 analysis, LDH release activity and ROS generation analysis, flow cytometry analysis, and nuclear staining test were performed to test the influence of CPS in cultured cells in vitro, meanwhile western blot was done to uncover the precise molecular mechanisms. 786-O renal cancer xenografts were builded to investigate the antitumor activity of CPS in vivo.
  
  
  
  We found treatment of CPS reduced proliferation of renal carcinoma cells, which could be attenuated by TRPV1 representative antagonist capsazepine (CPZ). CPS induced obvious apoptosis in renal carcinoma cells. These events were associated with substantial up-regulation of pro-apoptotic genes including c-myc, FADD, Bax and cleaved-caspase-3, -8, and -9, while down-regulation of anti-apoptotic gene Bcl2. Besides, CPS-treatment activated P38 and JNK MAPK pathways, yet P38 and JNK inhibitors afforded protection against CPS-induced apoptosis by abolishing activation of caspase-3, -8, and -9. Furthermore, CPS significantly slowed the growth of 786-O renal cancer xenografts in vivo.
  
  
  
  Such results reveal that CPS is an efficient and potential drug for management of human RCC.
authors.affiliation: Department of Urology, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Endodontics, Stomatology of Wuhan University, Wuhan, 430079, China.
authors.forename: Huangheng
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wangxinghuan@whu.edu.cn.
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. zhoujiajiejingzhou@126.com.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D045022:Lactate Dehydrogenases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D002211:Capsaicin
keywords: Apoptosis; Capsaicin; Caspases; MAPK; Renal cell carcinoma; TRPV1