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MG624, an α7‐nicotinic receptor antagonist suppresses the growth of human SCLC
Author(s) -
Shiflett Brandon S,
Brown Kathleen C,
Lau Jamie K,
Witte Ted R,
Hardman W Elaine,
Chen Yi C,
Luo Haitao,
Dasgupta Piyali
Publication year - 2011
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.25.1_supplement.792.6
Small cell lung cancer (SCLC) is characterized by rapid progression, early metastasis and low survival rates. Smoking has been correlated to 90% of all reported SCLC cases, suggesting that tobacco components like nicotine contribute to the pathophysiology of this disease. SCLCs have a functional cholinergic loop, and express nicotinic acetylcholine receptors (nAChRs). Our data shows that that long‐term exposure to nicotine stimulates the growth of the human SCLCs. The ablation of the α7‐nAChR by siRNA methodology suppressed the growth‐stimulatory effects of nicotine, indicating that nicotine stimulated the proliferation of human SCLC cells 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 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 chicken chorioallantoic membrane and in athymic mice models. Our data suggest that MG624 may have potential applications for the treatment of human SCLCs.