title: Curcumin reverses benzidine-induced cell proliferation by suppressing ERK1/2 pathway in human bladder cancer T24 cells.
abstract: Bladder cancer is one of the leading causes of cancer-related death in the world. Prolonged exposure to benzidine is a known cause of bladder cancer. Curcumin has been clinically used in chemoprevention and treatment of cancer. However, it remains unknown whether mitogen-activated protein kinase (MAPK) pathways are involved in curcumin-mediated protection from benzidine-associated promotive effects on bladder cancer. In our study, we found that benzidine increased the proliferation of human bladder cancer T24 cells, triggered transition of the cells from G1 to S phase, elevated the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) and decreased p21 expression. Meanwhile, exposure of T24 cells to benzidine resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2) pathway as well as activator protein 1 (AP-1) proteins. Treatment with ERK1/2 inhibitor U0126 or curcumin effectively abrogated benzidine-triggered cell proliferation and ERK1/2/AP-1 activation. These results suggested for the first time that curcumin in low concentrations played a protective role in benzidine-induced ERK1/2/AP-1 activation and proliferation of bladder cancer cells, therefore providing new insights into the pathogenesis and chemoprevention of benzidine-associated bladder cancer.
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Qi-Fei
authors.initials: QF
authors.lastname: Deng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Liang
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Xie
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China. Electronic address: yudx_urology@126.com.
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: cyzhong@njmu.edu.cn.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001560:Benzidines / Q000633:toxicity*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001560:Benzidines; C029876:benzidine; D003474:Curcumin
keywords: Benzidine; Bladder cancer; Cell proliferation; Curcumin; ERK1/2 pathway