The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells.
The specific binding of [125I]Tyr-Ala-hexarelin, a radiolabeled peptidyl GH secretagogue (GHS), has been investigated in nontumoral and neoplastic human lung tissues. This binding was very marked in nonendocrine lung carcinomas with values that were greater than found in either normal lung or in endocrine lung neoplasms. Tyr-Ala-hexarelin binding was also present in a human lung carcinoma cell line (CALU-1). [125I]Tyr-Ala-hexarelin binding to tumor membranes was displaced by peptidyl GHS (GHRP-6, hexarelin) and EP-80317, an hexarelin analog devoid of GH-releasing activity in vivo. In contrast, no competition was observed in the presence of the nonpeptidyl GHS MK-0677 and the endogenous ligand of the GHS-R1a ghrelin. GHS-R1a mRNA expression was found in 50% of endocrine lung tumors but was never seen in other nontumoral and neoplastic lung tissues nor in CALU-1. In these cells, hexarelin and EP-80317, but not ghrelin or MK-0677, caused a dose-dependent inhibition of IGF-II-stimulated thymidine incorporation and cell growth at concentrations close to their binding affinity. In conclusion, this study shows that inhibition of DNA synthesis and proliferation of CALU-1 cells is caused by peptidyl but not by nonpeptidyl GHS and ghrelin and suggests that this effect is likely to be mediated by a specific non-GHS-R1a receptor.
Ghè
Corrado
C
Department of Anatomy, University of Turin, Turin 10125, Italy.
Cassoni
Paola
P
Catapano
Filomena
F
Marrocco
Tiziana
T
Deghenghi
Romano
R
Ghigo
Ezio
E
Muccioli
Giampiero
G
Papotti
Mauro
M
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004701:Endocrine Gland Neoplasms / Q000378:metabolism; D005260:Female; D054439:Ghrelin; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D036361:Peptide Hormones; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013141:Spiro Compounds / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054439:Ghrelin; D007211:Indoles; D009842:Oligopeptides; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D013141:Spiro Compounds; C119142:tyrosyl-alanyl-hexarelin; C086184:hexarelin; D019382:Human Growth Hormone; C094817:ibutamoren mesylate