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 gro wth of various human cancers both in vivo and in vitro. GHRH, vasoactive in testinal 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 antagoni stic analogs of GHRH on the GHRH- and VIP-induced cAMP release from culture d human cancer cells in a superfusion system. Various human cancer cell lin es were exposed to human GHRH(1-29)NH2 (2-20 nM) or VIP (0.1-5 nM) repeated ly for 12 min or continuously for 96 min. GHRH antagonist MZ-5-156 at 100 t o 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 suppr ess the stimulatory effects of GHRH and VIP on the cAMP production of vario us cancer cells. Because cAMP is a potent second messenger controlling many intracellular functions, including the stimulation of cell growth, an inhi bition of autocrine/paracrine action of GHRH by the GHRH antagonists may pr ovide the basis for the development of new methods for cancer treatment. (C ) 1999 Elsevier Science Inc. AU rights reserved.