Memantine (a dual α7‐nAChR/NMDAR antagonist) displays anti‐angiogenic activity in human squamous cell lung cancer

Cigarette smoking accounts for 85% of squamous cell lung cancer (SCC‐L) in patients. Since SCC‐L is a highly angiogenic tumor, anti‐angiogenic therapies like Avastin have been investigated for the treatment of SCC‐L. However, the drawback of these therapies has been the incidence of pulmonary hemorrhage and extensive hemoptysis in SCC‐L patients. Nicotine, the addictive component of cigarettes, promotes angiogenesis in lung cancer via the α7‐nicotinic acetylcholine receptor (α7‐nAChR) subunit in human lung endothelial cells. Therefore, we conjectured that α7‐nAChR‐antagonists should display potent anti‐angiogenic and antitumor activity in SCC‐Ls. We observed that the α7‐nAChR is robustly expressed on human microvascular endothelial cells of the lung (HMEC‐Ls) and SCC‐L associated endothelial cells (STACE). With this background in mind, we tested the anti‐angiogenic activity of memantine (dual α7‐nAChR/NMDAR antagonist) in SCC‐Ls. Receptor binding assays have shown that the affinity of Memantine for α7‐nAChR is greater than NMDAR. Here we show that memantine attenuates nicotine‐induced angiogenesis in human microvascular endothelial cells of the lung (HMEC‐Ls). Furthermore, the α7‐nAChR antagonist memantine displayed potent antiangiogenic activity in the chicken chorioallantoic membrane (CAM) model. Memantine is an FDA approved drug, used in clinical practice to treat mild‐moderate Alzheimer's disease. It is well tolerated by patients and has a favorable side effect profile. Our studies are unique and innovative because they study, for the first time, the application of memantine in a non‐neuronal disease, namely lung cancer. Support or Funding Information Funding for our study was supported by an NIH R15‐AREA Grant (2R15CA161491‐02), Edwards Cancer Center Pilot grant, Cabell Huntington Hospital, Marshall University. This work was supported in part by the West Virginia IDeA Network of Biomedical Research Excellence (WV‐INBRE) grant GM103434 (PI: Dr. G. Rankin). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .