Multiple functions of the cholinesterase inhibiting polyalkylpyridinium salts extracted from the marine sponge, Haliclona sarai.

The interest on the Mediterranean sponge Haliclona sarai was raised some years ago by the fact that this sponge appears free from parasites and fouling organisms present in its environment. The study of such a feature was at the beginning due to the interest in finding new and efficient anti-fouling substances for applicative purposes. The characteristic was related to the expression of poly-alkylpyridinium salts (poly- APs), a mixture of two of 3-octylpyridinium polymers, including 29 and 99 monomeric units. The main effect of this compound was represented by the strong specific and non-toxic acetylcholinesterase inhibition in vitro. The substance was first tested for its effect on larval development and settling of incrusting organisms, such as Amphibalanus amphitrite. The experiments confirmed the ability of Poly-APs to prevent settlement of sessile organism, by impinging on the AChE activity. Acetylcholinesterase is an enzyme associated to the cholinergic signal system, but 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, and is present in some tumour cells and biopsies. Cytotoxicity tests on immortalized and primary cell lines derived from lung tumour (NSCLC) showed a poly-APS dose-dependent selective reduction of cell viability, statistically significant. The same cells, exposed to the poly-APS salts exhibited a loss in the mitochondrial potential, and positive response to apoptosis assays. What makes the poly-APS salts interesting as anticancer therapy adjuvant is that they, at the concentrations inducing apoptosis in tumour cells, seem to scarcely affect the viability of lymphocytes isolated from healthy patients. In this promising frame, the need emerges for the isolation of synthetic homologs of poly-APS molecules, in order to start a study for the therapeutical application of the drug. Key words: Lung Cancer, Acetylcholinesterase; Apoptosis; Cell Proliferation; Poly-APS 1 Introduction Nature has supplied several active anticancer agents (vinca alkaloids, anthracyclines, epipodophyllotoxin, and taxanes), which have significantly improved the