Phenethyl isothiocyanate sensitizes androgen-independent human prostate cancer cells to docetaxel-induced apoptosis in vitro and in vivo.
OBJECTIVE
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.


CONCLUSIONS
These results offer obligatory impetus to test PEITC-Docetaxel combination for the treatment of AIPC in a clinical setting.
Xiao
Dong
D
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Singh
Shivendra Vikram
SV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; C058305:phenethyl isothiocyanate