Antagonistic analogs of growth hormone releasing hormone (GHRH) inhibit cyclic AMP production of human cancer cell lines in vitro.
Antagonistic analogs of growth hormone-releasing hormone (GHRH) inhibit growth of various human cancers both in vivo and in vitro. GHRH, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide stimulate cyclic AMP (cAMP) release from various human cancer cell lines in vitro. Thus, in the present study, we investigated the effects of antagonistic analogs of GHRH on the GHRH- and VIP-induced cAMP release from cultured human cancer cells in a superfusion system. Various human cancer cell lines were exposed to human GHRH(1-29)NH2 (2-20 nM) or VIP (0.1-5 nM) repeatedly for 12 min or continuously for 96 min. GHRH antagonist MZ-5-156 at 100 to 200 nM concentration inhibited the GHRH- or VIP-induced cAMP release from mammary (MDA-MB-468), prostatic (PC-3), and pancreatic (SW-1990 and CAPAN-2) cancer cells. These results show that antagonistic analogs of GHRH suppress the stimulatory effects of GHRH and VIP on the cAMP production of various cancer cells. Because cAMP is a potent second messenger controlling many intracellular functions, including the stimulation of cell growth, an inhibition of autocrine/paracrine action of GHRH by the GHRH antagonists may provide the basis for the development of new methods for cancer treatment.
Csernus
V
V
Endocrine, Polypeptide and Cancer Institute, VA Medical Center, New Orleans, Louisiana 70112-1262, USA.
Schally
A V
AV
Groot
K
K
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C106656:MZ 5-156; D019382:Human Growth Hormone; D014660:Vasoactive Intestinal Peptide; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP