Phenethyl Isothiocyanate Sensitizes Androgen-Independent Human Prostate Cancer Cells to Docetaxel-Induced Apoptosis In Vitro and In Vivo

Abstract

Purpose The present study was undertaken to determine efficacy of phenethyl isothiocyanate (PEITC) for sensitization of androgen-independent human prostate cancer cells (AIPC) to Docetaxel-induced apoptosis using cellular and xenograft models. Methods Cell viability was determined by trypan blue dye exclusion assay. Microscopy and DNA fragmentation assay were performed to quantify apoptotic cell death in cultured cells. Protein levels were determined by immunoblotting. PC-3 prostate cancer xenograft model was utilized to determine in vivo efficacy of the PEITC and/or Docetaxel treatments. Results Pharmacologic concentrations of PEITC augmented Docetaxel-induced apoptosis in PC-3 and DU145 cells in association with suppression of Bcl-2 and XIAP protein levels and induction of Bax and Bak. The PEITC-Docetaxel combination was markedly more efficacious against PC-3 xenograft in vivo compared with PEITC or Docetaxel alone. Significantly higher counts of apoptotic bodies were also observed in tumor sections from mice treated with the PEITC-Docetaxel combination compared with PEITC or Docetaxel alone. The PEITC and/or Docetaxel-mediated changes in the levels of apoptosis regulating proteins in the tumor were generally consistent with the molecular alterations observed in cultured cells. Conclusion These results offer obligatory impetus to test PEITC-Docetaxel combination for the treatment of AIPC in a clinical setting.