Abstract 4322: Iron increases the invasiveness of prostate cancer cells in vitro: Mechanisms and inhibition by the antioxidant ebselen

Abstract

Abstract The effect of iron on PC-3 prostate cancer cell invasiveness was investigated using Neuroprobe filter membrane transmigration assays. PC-3 cells were pre-incubated with ferric ammonium citrate (FAC) for 6 hours. Excess iron was removed before the assay. The PC-3 cells were placed on an extracellular membrane preparation (Matrigel®) in the upper wells of the chamber and allowed to migrate onto the underside of a porous membrane that allowed cell transmigration. The number of cells migrating to the underside of the membrane was determined and used as a marker of cell invasion. Pre-treatment with 100 µM FAC caused a 4-fold increase in PC-3 cell invasion when measured at 24 hours (P< 0.05). The FAC concentrations that induced PC-3 invasion were 100 times smaller than concentrations which interfered with cell viability or proliferation rate. Western blot analysis suggested that the effect of FAC exposure on PC-3 cell invasion was mediated by p42/44 MAP kinase activity. Furthermore, the antioxidant ebselen, a hydrogen peroxide inhibitor, decreased FAC-induced PC-3 cell invasion. We also examined the mRNA expression of invasion-related genes using a cDNA array and found a positive correlation between the exposures to FAC and the invasion phenotype of prostate cancer cells. The data demonstrated that the upregulation of genes, such as fractalkine and plasminogen, after FAC treatment may be associated with iron-induced invasion of prostate cancer. Our data suggest that iron overload may be detrimental to patients with prostate cancer and that the effect of iron on invasion may be inhibited by ebselen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4322. doi:1538-7445.AM2012-4322