Is α7-nAChR a Possible Target for Lung Cancer and Malignant Pleural Mesothelioma Treatment?

Alfredo Cesario, Patrizia Russo, Candida Nastrucci, Pierluigi Granone

doi:10.2174/138945012800398900

Abstract

This paper discusses the potential therapeutic effect of α7-nAChR antagonists for NSCLC (non small cell lung cancer) and MPM (malignant pleural mesothelioma). This therapeutic approach is based on the experimental observations that: (a) functional α7-nAChR are expressed in NSCLC and MPM cells, (b) the activation of these receptors by agonists, namely nicotine, induces cell proliferation and inhibits apoptosis, whereas antagonists have a pro-apoptotic effect. Among competitive α7-nAChR antagonists, d-tubocurarine and -cobratoxin (α-CbT), from the snake venom of Naja, emerged as possible drug candidates. However, some aspects of the samples must be particularly taken into account, such as the particular nature of the sample. Thus, when using natural compounds purified from snake venom, it is important to take into account the factors such as whether the venom sample was derived from different animals, purified by different methods, or contained contaminants of the same molecular weight. Finally, biological activity may be different for different batches, which could also have been stored under different conditions (e.g. temperature, dilution, suspension medium etc.). These factors, affecting the experimental results, are also discussed.

Keywords: NSCLC, MPM, d-tubocurarine, cobratoxin, apoptosis, antineoplastic effect, tissue homeostasis, smoking, lung cancer, Bungarotoxin