Induction of Apoptosis of Bladder Cancer Cells by Zinc-Citrate Compound

Purpose: Zinc is one of the trace minerals in the body and is known to have an anticancer effect by inducing apoptosis in prostate cancer. We aimed to investigate the anti-proliferative effects of a zinc-citrate compound in bladder cancer. Materials and Methods: A bladder cancer cell line (MBT-2) was treated with a zinc-citrate compound at different time intervals and concentrations. Mitochondrial (m)-aconitase activity was determined by use of the aconitase assay. DNA laddering analysis was performed to investigate apoptosis of MBT-2 cells. The molecular mechanism of apoptosis was investigated by Western blot analysis of p53, p21(waf1), Bcl-2, Bcl-xL, and Bax and also by caspase-3 activity analysis. Results: Treatment with the zinc-citrate compound resulted in a time-and dose-dependent decrease in cell number of MBT-2 cells. M-aconitase activity was significantly decreased. DNA laddering analysis indicated apoptosis of MBT-2 cells. The zinc-citrate compound increased the expression of p21waf1 and p53 and reduced the expression of Bcl-2 and Bcl-xL proteins but induced expression of Bax protein. The zinc-citrate compound induced apoptosis of MBT-2 cells by activation of the caspase-3 pathway. Conclusions: We have shown that a zinc-citrate compound induces apoptotic cell death in a bladder cancer cell line, MBT-2, by caspase-3 activation through up-regulation of apoptotic proteins and down-regulation of antiapoptotic proteins.