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Curcumin Reverses Benzidine-Induced Epithelial-Mesenchymal Transition via Suppression of ERK5/AP-1 in SV-40 Immortalized Human Urothelial Cells

Curcumin Reverses Benzidine-Induced Epithelial-Mesenchymal Transition via Suppression of ERK5/AP-1 in SV-40 Immortalized Human Urothelial Cells

Zhiqi Liu, Jie Liu, Li Zhao, Hao Geng, Jiaxing Ma, Zhiqiang Zhang, Dexin Yu, Caiyun Zhong

Int J Oncol. 2017 Apr;50(4):1321-1329.

PMID: 28259934

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1234480502	XMD8-92		1234480-50-2	Price

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