Bcl-2-independent induction of apoptosis by neuropeptide receptor antagonist in human small cell lung carcinoma cells.
The broad-spectrum antagonist of neuropeptide receptor, [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P, induced apoptosis selectively in human small cell lung carcinoma (SCLC) cells, which express gastrin-releasing peptide receptor, but not in other types of tumor cells as well as normal cells. The addition of gastrin-releasing peptide or bombesin and the inhibitor of caspase-3 suppressed [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P-induced apoptosis. Moreover, [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P-induced apoptosis was not suppressed by Bcl-2 over-expression. Thus, blockage of gastrin-releasing peptide receptor-mediated signaling may provide a novel therapeutic option in SCLC which has become resistant to conventional chemotherapeutic agents.
Matsumoto
Y
Y
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Kawatani
M
M
Simizu
S
S
Tanaka
T
T
Takada
M
M
Imoto
M
M
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D019169:Jurkat Cells; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019253:Proto-Oncogene Proteins c-bcl-2; D018004:Receptors, Bombesin; D013373:Substance P; D019886:Gastrin-Releasing Peptide; C045800:substance P, Phe(5)-Trp(7,9)-Leu(11)-; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases