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The α7‐nicotinic receptor antagonist induces robust apoptosis in human SCLC
Author(s) -
Brown Kathleen C.,
Lau Jamie K.,
Dom Aaron M.,
Shiflett Brandon S.,
Witte Theodore R.,
Hardman W. Elaine,
Luo Haitao,
Chen Yi Charlie,
Carpenter A. Betts,
Dasgupta Piyali
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.397.4
Subject(s) - nicotine , tunel assay , apoptosis , nicotinic agonist , receptor , cancer research , antagonist , nicotinic acetylcholine receptor , acetylcholine receptor , pharmacology , biology , receptor antagonist , endocrinology , medicine , chemistry , biochemistry
Small cell lung cancer (SCLC) is characterized by rapid progression, early metastasis 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 nicotinic acetylcholine receptors (nAChRs). Our data shows that long‐term exposure to nicotine stimulates the growth of the human SCLCs via the α7‐nAChR subtype. 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 assays. Furthermore, the administration of MG624 suppressed nicotine‐induced growth of H69 human SCLC xenografts in chicken chorioallantoic membrane and in athymic mice models. Immunohistochemical staining of the H69 tumors isolated from MG624‐treated athymic mice showed extensive apoptosis. Our data suggest that MG624 may have potential applications for the treatment of human SCLCs.