MG624, a synthetic small molecule alpha7 receptor antagonist, inhibits growth of human small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is characterized by early dissemination, aggressive clinical course and low survival rates. Smoking is correlated to 90% of all reported SCLC cases, suggesting that tobacco components like nicotine contribute to the pathophysiology of this disease. Nicotine promotes the proliferation of human lung cancer cells via the α7‐nicotinic acetylcholine receptors (α7‐nAChRs). Therefore, we hypothesized that α7‐nAChR antagonists should be useful in attenuating the growth of human SCLCs. We observed that the small molecule α7‐nAChR antagonist MG624 induced robust apoptosis in human SCLC cells as measured by TUNEL and caspase‐3 cleavage assay. Furthermore, the administration of MG624 suppressed nicotine‐induced growth of H69 human SCLC xenografts in athymic mice models. Immunohistochemical staining of the H69 tumor sections isolated from MG624‐treated from athymic mice show the presence of apoptotic bodies. Our data suggest that MG624 may have potential applications for the treatment of human SCLCs.