A somatostatin analogue inhibits MAP kinase activation and cell proliferation in human neuroblastoma and in human small cell lung carcinoma cell lines.
Somatostatin possesses antisecretory and antiproliferative activity on some human tumors. We herein report that, in a human neuroblastoma cell line, the somatostatin analogue BIM 23014 inhibited mitogen-activated protein (MAP) kinase activity stimulated by either insulin-like growth factor-1, whose receptor bears a tyrosine kinase, or carbachol, which acts at a G-protein coupled receptor. In a human small cell lung carcinoma line BIM inhibited serum-stimulated MAP kinase activation. These inhibitory actions occur in a dose range quite similar to that observed for suppression of proliferation induced by the analogue in the same cell lines. The decrease in cAMP elicited by the analogue in the two cell lines is not responsible for its inhibitory action on MAP kinase and cell growth. Moreover, the analogue did not modify intracellular [Ca2+] and pH. An involvement of a phosphatase activity is suggested.
Cattaneo
M G
MG
Department of Pharmacology, University of Milan, Italy.
Amoroso
D
D
Gussoni
G
G
Sanguini
A M
AM
Vicentini
L M
LM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D015398:Signal Transduction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D002217:Carbachol; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium