Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells.
The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investigated. Corticotropin-releasing factor increased the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated the cAMP levels approximately eleven-fold using NCI-H345 cells and increased the gastrin-releasing peptide (GRP) secretion rate by approximately 70%. Similarly, sauvagine, a structural analogue of CRF, elevated the cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-helical CRF(9-41). Corticotropin-releasing factor had no effect on cytosolic calcium but stimulated [3H]arachidonic acid release from NCI-H1299 cells with an ED50 of 30 nM. The increase in [3H]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 microM alpha-helical CRF(9-41). Also, CRF stimulated the clonal growth of NCI-H345 and H720 cells and the growth increase caused by CRF was reversed by alpha-helical CRF(9-41). These data suggest that CRF may be a regulatory peptide in lung cancer.
Moody
T W
TW
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.
Zia
F
F
Venugopal
R
R
Korman
L Y
LY
Goldstein
A L
AL
Fagarasan
M
M
D029845:Amphibian Proteins; D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019886:Gastrin-Releasing Peptide; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D029845:Amphibian Proteins; D010446:Peptide Fragments; D036361:Peptide Hormones; D010455:Peptides; D016718:Arachidonic Acid; C025727:sauvagine; D019886:Gastrin-Releasing Peptide; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D000242:Cyclic AMP; D002118:Calcium