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Multiple functions of the cholinesterase inhibiting polyalkylpyridinium salts extracted from the marine sponge, Haliclona sarai
Garaventa, Francesca ...
The interest on the Mediterranean sponge HaUc/ona sarai was raised some years ago by the fact that this sponge appears free from parasites and fouling organi sms 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 (polyAPs), a mixture of two of 3-octylpyridinium polymers, including 29 and 99 monomeric units. The main effect ofthis com pound was represented by the strong specific and non-toxic acetylcholinesterase inhibition in vi/ro. The substance was first tested for its effect on larval development and settling of incrusting organisms, such asAmphibalanus 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 celI-to-celI communication driving embryonic development and in the regulation of several celIular features, such as apoptosis and celI movements, and is present in some tumour celIs and biopsies. Cytotoxicity tests on immortalized and primary celI lines derived from lung tumour (NSCLC) showed a poly-APS dose-dependent selective reduction of celI viability, statisticalIy significant. The same celIs, exposed to the poly-APS salts exhibited a los s 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 celIs, 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.
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