Antiproliferative Effects of Zinc-Citrate Compound on Hormone Refractory Prostate Cancer

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 analysis of P53, P21w^fl, 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 P21wall and P53, and reduced the expression 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.

Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge

Objective:To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge.(SM)on the castration-resistant prostate cancer(CRPC)cell line DU-145 in vitro and in vivo.Methods:Prostate cancer cell line(DU-145)and normal prostate cell line(RWPE-1)were treated with SM at different concentrations(3.125,12.5,25 and 50μg/mL)to investigate the antiproliferative effects.DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells.Molecular mechanism was investigated by Western blot analysis of p53,Bcl-2,prostate specific antigen(PSA),and androgen receptor(AR).Six-week-old male BALB/c nude mice were randomly divided into normal control group(n=101)and treated group(n=101)which administered 500 mg/kg SM for 2 weeks.Tumor volumes were measured.Results:Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1.DNA laddering analysis indicated the apoptosis of DU-145 cells.Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins.The levels of PSA were considerably reduced in SM-treated group compared to the controls,and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA.In the tumour xenograft study,SM given once a day for 2 weeks significantly inhibited tumour growth.Conclusion:SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.