Small cell lung cancer bombesin receptors are antagonized by reduced peptide bond analogues.
The potency of 3 reduced peptide bond analogues of bombesin (BN) was investigated using small cell lung cancer (SCLC) cell lines. (Psi13,14, Leu14)BN, (Psi9,10, Leu14)BN and (Psi12,13, Leu14)BN inhibited specific binding of 125I-GRP with IC50 values of 15, 90, and 600 nM. (Psi13,14, Leu14)BN and (Psi9,10, Leu14)BN did not elevate cytosolic Ca2+ levels but antagonized the increase in cytosolic Ca2+ caused by BN. (Psi13,14, Leu14)BN antagonized the clonal growth of SCLC cells caused by BN. These data indicate that reduced peptide bond analogues may disrupt the autocrine growth cycle of SCLC cells by functioning as BN receptor antagonists.
Mahmoud
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Dept. of Biochemistry, George Washington University School of Medicine & Health Sciences, Washington, DC 20037.
Palaszynski
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E
Fiskum
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G
Coy
D H
DH
Moody
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TW
D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002999:Clone Cells / Q000187:drug effects; D019886:Gastrin-Releasing Peptide; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010455:Peptides; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D002118:Calcium