Previous studies have shown that the
cholinergic system plays a pivotal rule in
small cell lung cancer (SCLC) cell growth through an autocrine loop that activates the nicotinic
cholinergic receptor, which together with the activation of this receptor by
nicotine links SCLC evolution with tobacco use.
Non-small cell lung cancer (NSCLC) is the most common form of
lung cancer and is also linked to tobacco use. Here we describe the presence of molecules of the
cholinergic system in NSCLC samples and cell lines and investigate the implications of the
cholinergic system in cell growth regulation. Cholino-
acetyltransferase (ChAT),
vesicular acetylcholine transporter (VAChT) and
acetylcholinesterase (AChE) were observed in NSCLC
tumor biopsies and in NSCLC cell lines. Polymeric alkylpyridinium
salts (
poly-APS) are AChE inhibitors isolated from the
crude extract of the marine sponge, Reniera sarai. These metabolites were characterized as a mixture of two
polymers of 3-octylpyridinium, including 29 and 99 monomeric units. Exposure of normal lung fibroblast and NSCLC cell lines to
poly-APS revealed a selective cytotoxicity for
cancer cells as compared to the normal fibroblast cell lines. FACS analysis indicated
poly-APS induced apoptosis in NSCLC cells but not in normal lymphocytes. Non-toxic doses of
poly-APS also potently reduced NSCLC cell-cell adhesion in
suspension cultures. The limited toxicity of
poly-APS on normal cells was confirmed by injection in the caudal vein of mice. No overt effects on health parameters, such as
weight gain and physical behavior, were observed, and histological analysis of major organs did not reveal differences between the treated animals as compared to controls. These data demonstrate that NSCLC cells express
cholinergic molecules that may be involved in cell growth regulation and that the
cholinesterase inhibitor,
poly-APS, shows selective toxicity toward NSCLC cells while having no apparent toxicity towards normal cells and tissue in vitro and in vivo.