['In castrate resistant prostate cancer cells we investigated the cytotoxic effect of simvastatin and the mechanism involved.', 'After treating PC3 and DU-145 cells with simvastatin, cell viability and apoptosis were determined using tetrazolium salt based colorimetric assay and annexin-V-fluorescein isothiocyanate/propidium iodide double staining assay, respectively. To determine whether simvastatin affects the nuclear factor-κB pathway, we assessed IκBα and phosphorylated IκBα expression, and p65 and phosphorylated p65 subcellular localization by Western blot analysis. Also, changes in nuclear factor-κB transcriptional activity were assessed using a luciferase reporter assay.', 'After treating PC3 and DU-145 cells with 0, 20 or 40 μM simvastatin for 24, 48 or 72 hours, the proportion of viable cells decreased and the proportion of apoptotic cells increased in a dose and time dependent manner. Western blot analysis showed that simvastatin inhibited IκBα phosphorylation and degradation. It also demonstrated that simvastatin increased p65 protein levels in cytoplasmic fractions and decreased phosphorylated p65 protein levels in nuclear fractions but did not change p65 protein levels in cytoplasm. Luciferase reporter assay showed that simvastatin dose dependently reduced nuclear factor-κB activity. Reverse transcriptase-polymerase chain reaction and Western blot revealed that simvastatin inhibited nuclear factor-κB regulated cIAP-1 and 2, cFLIP-S and XIAP expression in dose and time dependent fashion.'] Does simvastatin induce apoptosis in castrate resistant prostate cancer cells by deregulating nuclear factor-κB pathway?