Curcumin Reverses Benzidine-induced Cell Proliferation By Suppressing ERK1/2 Pathway In Human Bladder Cancer T24 Cells

Objective: Benzidine, which belongs to aromatic amines, is classified as a known human carcinogen which is closely associated with bladder cancer. However, little knowledge is available concerning its cancer-promoting activities. The present study described here aimed to investigate the effects of benzidine on ERK1/2/AP-1 activation and cell cycle regulation in human bladder carcinoma T24 cells and determine whether curcumin has a protective role in benzidine-induced alteraions. Methods:Exposing T24 cells to various concerntions of benzidine with or without U0126 or curcumin for 6 days, cell viability was evaluated by MTT assay and cell cycle was detected by flow cytometry assay subsequently. Expressions of ERK1/2/AP-1 proteins, cyclin D1, PCNA and p21 were also assessed by western blot and RT-PCR. Results:Low concentrations of benzidine(0.001, 0.005 and 0.01 μΜol/l) promoted cell proliferation and enhanced ERK1/2 phosphorylation in T24 cells. Distinct expressions of AP-1 proteins were also observed. Furthermore, we found that treating T24 cells with benzidine induced the up-regulation of cyclin D1 and PCNA as well as down-regulation of p21. Afterwards, cells were co-treated with U0126(10 μΜol/l) or curcumin(5 μΜol/l) for 6 days. Then we found benzidine-induced alteraions in T24 cells were reversed. Conclusion:These findings indicated that low concentrations of benzidine enhanced cell proliferation in T24 cells. Inhibition of ERK1/2 pathway by U0126 suppressed benzidine-induced cell proliferation. Curcumin may serves as an effective agent against benzidine-associated bladder cancer.