title: Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells.
abstract: Overexposure to benzidine has been manifested as an important cause of bladder cancer. However, the molecular mechanism of benzidine-induced malignancy is still insufficiently interpreted. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in embryonic development as well as initiation and development of epithelium-originated malignant tumors. The role of extracellular regulated protein kinase 5 (ERK5) in benzidine-meditated bladder cancer development has not been explored. In the present study, we explored the role of ERK5/AP-1 pathway in benzidine-induced EMT in human normal urothelial cells and the intervention effect of curcumin on bezidine-induced EMT. We found that benzidine-induced EMT in SV-40 immortalized human urothelial cells (SV-HUC-1) at low concentrations. We detected that ERK5/AP-1 pathway was notably activated. Specific ERK5 inhibitor, XMD8-92 was applied to determine the role of ERK5 in benzidine-induced EMT. Results indicated that XMD8-92 reversed the EMT process. Furthermore, curcumin effectively attenuated benzidine-induced urocystic EMT by suppressing ERK5/AP-1 pathway. In conclusion, the present study revealed the positive role of ERK5/AP-1 in benzidine-provoked urocystic EMT and the curcumin promising use in bladder cancer prevention and intervention via ERK5/AP-1 pathway.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001560:Benzidines / Q000633:toxicity*; D001570:Benzodiazepinones / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D001743:Urinary Bladder; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D019459:Urothelium / Q000166:cytology
chemical_list: D000970:Antineoplastic Agents; D001560:Benzidines; D001570:Benzodiazepinones; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; C568790:XMD 8-92; C029876:benzidine; D011494:Protein Kinases; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7; D003474:Curcumin