Objective:To investigate the antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer (HRPC).Methods:HRPC cell line (DU145) and normal prostate cell line (RWPE-1) were treated with zinc,citrate and zinc-citrate compound at different time intervals and concentrations to investigate the effect of zinc-citrate compound.Mitochondrial (m)-aconitase activity was determined using aconitase assay.DNA laddering analysis was performed to investigate apoptosis of DU145 cells.Molecular mechanism of apoptosis was investigated by Western blot analys s of P53,P21waf1,Bcl-2,Bcl-xL and Bax,and also caspase-3 activity analysis.Results:Treatment with zinc-citrate compound resulted in a time- and dose-dependent decrease in cell number of DU145 cells in comparison with RWPE-1.M-aconitase activity was significantly decreased.DNA laddering analysis indicated apoptosis of DU145 cells.Zinc-citrate compound increased the expression of P21waf1 and P53,and reduced the express on of Bcl-2 and Bcl-xL proteins but induced the expression of Bax protein.Zinc-citrate compound induced apoptosis of DU145 cells by activation of the caspase-3 pathway.Conclusion:Zinc-citrate compound can induce apoptotic cell death in DU145,by caspase-3 activation through up-regulation of apoptotic proteins and down-regulation of antiapoptotic proteins.