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-Arg(1), D-Phe(5) , D-Trp(7,9), Leu(11)]substance P, induced apoptosis selectively in human s mall cell lung carcinoma (SCLC) cells, which express gastrin-releasing pept ide 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 o f caspase-3 suppressed [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]substance P -induced apoptosis. Moreover, [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]subs tance P-induced apoptosis was nor suppressed by Bcl-2 overexpression. Thus, blockage of gastrin-releasing peptide receptor-mediated signaling may prov ide a novel therapeutic option in SCLC which has become resistant to conven tional chemotherapeutic agents.