Is α7-nAChR a possible target for lung cancer and malignant pleural mesothelioma treatment?
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.
Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Via di Val Cannuta 247-249, 00166 Rome, Italy.
Alfredo
A
Cesario
Patrizia
P
Russo
Candida
C
Nastrucci
Pierluigi
P
Granone
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D016503:Drug Delivery Systems; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008654:Mesothelioma / Q000188:drug therapy / Q000473:pathology; D009538:Nicotine / Q000009:adverse effects; D018722:Nicotinic Agonists / Q000009:adverse effects; D018733:Nicotinic Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000473:pathology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000970:Antineoplastic Agents; C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012910:Snake Venoms; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine