Since the first \u201880s, we found that some tumor types, and in particular lung tumors present increase, or
generally change in acetylcholinesterase activity. Acetylcholinesterase is an enzyme associated to the cholinergic signal
system, whose classic role is to remove acetylcholine from the receptors. Nevertheless, it is also involved in cell-to-cell
communication driving embryonic development and in the regulation of several cellular features, such as apoptosis and
cell movements. The presence of molecules related to the cholinergic signal system in the healthy and carcinogenic lung
tissues, raised the hypothesis that substances inhibiting or affecting the cholinergic signaling system could exert an anticancer
action at least in these tissues. Cytotoxicity tests on immortalized and primary cell lines derived from lung tumor
(NSCLC) showed an AChE inhibition-dependent selective reduction of cell viability, statistically significant. The same
cells, exposed to non toxic AChE inhibitors exhibited a loss in the mitochondrial potential, characteristic of the early
apoptotic events and showed positive response to the annexin V assay, and to the T-terminal assay, that are specific
features of the apoptotic event. Moreover, three-dimensional cell cultures (spheroids) of tumor cells, on exposure to
AChE inhibitors show a decrease in the membrane-linked oligosaccharides, that are responsible for the adhesivity of the
metastatic cells. In this promising picture, the need emerges of further studies aimed at understanding the effects of
AChE inhibition on the regulation of acetylcholine release and the effects of AChE inhibitors on the functioning of
acetylcholine receptors
