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 antibiotic, and cathepsin D (Cat.D), a lysosomal protease, in prostate cancer proliferation. 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 effect on Cat.D in these cancer cells was assessed by Western blots and compared with Cat.D expressed in clinical prostate specimens (n = 55). BFA profoundly (> 70%) inhibited the growth of all three cancer cell lines. Western blots revealed that expression of procathepsin D (Pro.Cat.D) was markedly increased with BFA, whereas actively proliferating (control) cells greatly exhibited 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 of Cat.D maturation (activation), suggesting a possible role of Cat.D in prostate cancer proliferation/development.
Konno
S
S
Department of Urology, New York Medical College, Valhalla 10595, USA. sensuke_konno@nymc.edu
Cherry
J P
JP
Mordente
J A
JA
Chapman
J R
JR
Choudhury
M S
MS
Mallouh
C
C
Tazaki
H
H
D000935:Antifungal Agents / Q000494:pharmacology*; D020126:Brefeldin A / Q000494:pharmacology*; D002402:Cathepsin D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000935:Antifungal Agents; D020126:Brefeldin A; D002402:Cathepsin D