Effects of brefeldin A on androgen receptor-mediated cellular responses inhuman prostatic carcinoma LNCaP cells

An antiviral antibiotic, brefeldin A (BFA), is known as an inhibitor of int racellular protein transport and is presumed to have antitumor activity. We examined its effects on androgen-responsive cell growth, prostate-specific antigen (PSA) synthesis, and androgen receptor (AR) expression in human pr ostatic carcinoma LNCaP cells. In a dose of 30 ng/mL, BFA suppressed cell g rowth by >75% compared with control. Cell cycle analysis indicated that thi s growth inhibition was in part attributed to arrest at the G(1)-S transiti on phase. 5 alpha-Di-hydrotestosterone (DHT) was unable to reverse the BFA- induced growth suppression; instead, DHT-stimulated cell growth was almost completely abolished by BFA, As well, DHT-stimulated PSA synthesis and secr etion were dramatically reduced by BFA, Western immunoblots showed that BFA drastically reduced AR expression to approximately 10% of control by 72 ho urs, and this downregulation of AR was apparent at 6 hours after BFA treatm ent, These studies demonstrate that BFA is a potent modulator, capable of i nhibiting cell growth and PSA synthesis/secretion, in LNCaP cells, presumab ly through its ability to modulate AR expression.