Finasteride induces apoptosis via Bcl-2, Bcl-xL, Bax and caspase-3 proteins in LNCaP human prostate cancer cell line.
We investigated the effects of finasteride, a 5alpha-reductase inhibitor, on cell death machinery through the induction of apoptosis in an in vitro model for prostate cancer. Finasteride treatment of the LNCaP hormone-dependent human prostate cancer cell line caused the loss of cell viability and accelerated apoptosis in a concentration-dependent manner. The contents of immunoreactive procaspase-3 were examined by immunoblot analysis and the results suggest that the apoptosis induced by finasteride involves the increase of caspase-3 activity. Early cell changes that occur during apoptosis are associated with mitochondrial changes mediated by members of the Bcl-2 family of proteins. Therefore, Bcl-2, Bcl-xL and Bax were evaluated by the Western blot analysis. The immunoreactivity for pro-apoptotic Bax was markedly increased whereas antiapoptotic Bcl-2 and Bcl-xL expression was significantly reduced after incubation of cells with finasteride. These findings suggest that finasteride induces apoptosis in LNCaP cells via proteins of the Bcl-2 and caspase family.
Golbano
Jesús M
JM
Servicio de Urología, Hospital General Universitario de Guadalajara, Guadalajara, Spain.
Lóppez-Aparicio
Pilar
P
Recio
María N
MN
Pérez-Albarsanz
Miguel A
MA
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology*; D045744:Cell Line, Tumor; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000502:physiology*; D051020:bcl-X Protein / Q000502:physiology*
D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D018120:Finasteride; D042944:Cholestenone 5 alpha-Reductase; D053148:Caspase 3