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Studies on a promising anticancer molecule of marine origin : results of an interdisciplinary study
Zovko, Ana ...
Poly-APS, a mixture of two of 3-octylpyridinium polymers, including 29 and 99 monomeric units, extracted from the Mediterranean sponge, Haliclona (Reniera) sarai, was demonstrated to exert strong ...specific and non-toxic acetylcholinesterase inhibition in vitro. Since the first '80s, we found that some tumour types, and in particular lung tumours present overexpression of acetylcholinesterase activity. Acetylcholinesterase is an enzyme associated tothe cholinergic signal system, but is also involved in cell-tocell 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 primarycell 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 inthe mitochondrial potential, showed positive response to the annexin V assay, and to the T-terminal assay, that are specific markers of the apoptoticevent. What makes the poly-APS salts promising as anticancer therapy adjuvant is that they, at the concentrations inducing apoptosis in tumour cells, do not affect the viability of lymphocytes isolated from healthy patients. Moreover, three-dimensional cell cultures (spheroids) of tumour cells, on exposure to poly-APS show a decrease in the membrane-linked oligosaccharides, that are responsible for the adhesivity of the metastatic cells. Moreover, no effects were demonstrated on healthy organs, such as heart, liver, kidney of mice treated by poly-APS, and in vivo tumours showed amass and cellular density significantly reduced. In this promising frame, theneed 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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