title: Ursolic acid induces ER stress response to activate ASK1-JNK signaling and induce apoptosis in human bladder cancer T24 cells.
abstract: Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We show that ursolic acid induces a significant ER stress response in cultured human bladder cancer T24 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3 activation in T24 cells. Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex formation to activate pro-apoptotic ASK1-JNK signaling. We suggest that ER stress contributes to ursolic acid's effects against bladder cancer cells.
authors.affiliation: Department of Urology, the Military General Hospital of Beijing PLA, Beijing 100700, China. qingyouzheng@yahoo.com
authors.forename: Qing-you
authors.initials: QY
authors.lastname: Zheng
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Li
authors.forename: Feng-suo
authors.initials: FS
authors.lastname: Jin
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.forename: Guo-hui
authors.initials: GH
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Zang
authors.forename: Xing
authors.initials: X
authors.lastname: Ai
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3; D002934:Cinnamates; D004722:Endoribonucleases; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D047992:TNF Receptor-Associated Factor 2; D013890:Thiourea; D051742:Transcription Factor CHOP; D014315:Triterpenes; D019892:eIF-2 Kinase; D000097245:Ursolic Acid; C000606775:BCL2L11 protein, human; C497249:DDIT3 protein, human; C496827:salubrinal; C403982:ERN2 protein, human