PACAP(6-38) inhibits the growth of prostate cancer cells.
The effects of pituitary adenylyl cyclase activating polypeptide (PACAP) analogs on prostate cancer cell lines was investigated. 125I-PACAP-27 bound with high affinity to PC-3 cells (Kd = 10 nM) to a single class of sites (Bmax = 30000/cell). By RT-PCR, a major 305 bp band was observed using cDNA derived from PC-3, LNCaP or DU-145 cells. Specific 125I-PACAP binding was inhibited with high affinity by PACAP-27, PACAP-38 and PACAP(6-38) (IC50 values of 15, 10 and 300 nM, respectively) but not by PACAP(28-38). PACAP elevated cAMP and the increase caused by PACAP-27 was reversed by PACAP(6-38). PACAP transiently increased c-fos gene expression and the increase in c-fos mRNA was reversed by PACAP(6-38). PACAP-27 stimulated colony formation in PC-3 cells, whereas PACAP(6-38) reduced colony number and size. In nude mice bearing PC-3 xenografts, PACAP(6-38) significantly slowed tumor growth. These data suggest that biologically active type 1 PACAP receptors are present on human prostate cancer cells and that prostate cancer cell growth is inhibited by PACAP(6-38).
Leyton
J
J
Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA.
Coelho
T
T
Coy
D H
DH
Jakowlew
S
S
Birrer
M J
MJ
Moody
T W
TW
D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D016762:Genes, fos; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP