Is α7-nAChR a possible target for lung cancer and malignant pleural mesothelioma treatment?

Curr Drug Targets. 2012 May;13(5):688-94. 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.

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Delivery Systems
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Mesothelioma / drug therapy
  • Mesothelioma / pathology
  • Nicotine / adverse effects
  • Nicotinic Agonists / adverse effects
  • Nicotinic Antagonists / isolation & purification
  • Nicotinic Antagonists / pharmacology*
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / pathology
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Snake Venoms / chemistry
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Antineoplastic Agents
  • Chrna7 protein, human
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Snake Venoms
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine