Role of cathepsin D in prostatic cancer cell growth and its regulation by brefeldin A

We investigated a possible relationship between brefeldin A (BFA), an antib iotic, and cathepsin D (Cat.D), a lysosomal protease, in prostate cancer pr oliferation. Effects of BFA (30 ng/ml) were examined on the growth of three human prostatic cancer cell lines, PC-3, DU-145, and LNCaP cells. Its effe ct on Cat.D in these cancer cells was assessed by Western blots and compare d with Cat.D expressed in clinical prostate specimens (n = 55). BFA profoun dly (> 70%) inhibited the growth of all three cancer cell lines. Western bl ots revealed that expression of procathepsin D (Pro.Cat.D) was markedly inc reased with BFA, whereas actively proliferating (control) cells greatly exh ibited mature Cat.D. Analysis of prostate specimens then showed predominant Pro.Cat.D expression in non-cancerous tissues while also showing enhanced expression of mature Cat.D in all cancer specimens. Therefore, BFA-induced growth inhibition in prostatic cancer cells is associated with a blocking o f Cat.D maturation (activation), suggesting a possible role of Cat.D in pro state cancer proliferation/development.