Substance P analogues function as bombesin receptor antagonists and inhibit small cell lung cancer clonal growth.
Human small cell lung cancer (SCLC) produces and secretes BN/GRP (bombesin/gastrin releasing peptide). Because BN stimulates the growth of SCLC cells and these cells have receptors for BN-like peptides, it is important to define agents which disrupt this self-promoting autocrine growth cycle. Here, substance P analogues were evaluated as BN receptor antagonists using SCLC cell lines. (D-Arg1, D-Pro2, D-Trp7.9, Leu11) substance P [(APTTL)SP] was one of the more potent analogues tested in inhibiting BN-like peptide receptor binding with an IC50 value of 1 microM. Micromolar concentrations of (APTTL)SP antagonized BN receptor mediated elevation of cytosolic Ca2+ levels and decreased the colony formation in soft agarose. These data suggest that SP analogues function as SCLC BN receptor antagonists and may be useful in disrupting the autocrine growth function of BN-like peptides.
Bepler
G
G
Philipps University Marburg, Department of Internal Medicine, Marburg, West Germany.
Zeymer
U
U
Mahmoud
S
S
Fiskum
G
G
Palaszynski
E
E
Rotsch
M
M
Willey
J
J
Koros
A
A
Cuttitta
F
F
Moody
T W
TW
D001839:Bombesin / Q000378:metabolism; D018288:Carcinoma, Small Cell; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D006801:Humans; D008175:Lung Neoplasms; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D013373:Substance P; D001839:Bombesin