Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation

BJU International
Jonathan P CoxonKay W Colston

Abstract

To investigate effects of zoledronic acid on apoptosis and adhesion to mineralized matrix in prostate cancer cells, to quantify these actions, and to elucidate some of the underlying molecular mechanisms, in terms of dependence on caspase activation and involvement of protein prenylation. DU145 and PC-3 prostate cancer cell lines were used; cells were treated with zoledronic acid, with or without several other reagents, to investigate its mechanism of action. Apoptosis was detected using a cell-death detection enzyme-linked immunosorbent assay. Adhesion was measured by seeding cells onto mineralized dentine inserts for 24 h, and counting cells after washing. Apoptosis depended on time and dose; there was significant apoptosis with higher concentrations of zoledronic acid (100 micromol/L) after 24 h of exposure, and in DU145 cells with concentrations as low as 1 micromol/L after 72 h of exposure. The apoptotic effect was diminished by co-treating with a broad-spectrum caspase inhibitor, Z-VAD-FMK. Zoledronic acid at 1 micromol/L also significantly inhibited cell adhesion to the mineralized matrix. The lipid isoprenoid analogue geranylgeraniol reduced the apoptotic and anti-adhesive effects of zoledronic acid to a greater degree ...Continue Reading

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