Studies on a promising anticancer molecule of marine origin: results of an interdisciplinary study

作者: M. G. Aluigi , S. Trombino , K. Sepcic , L. Paleari , S. Ferrando

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摘要: Poly-APS, a mixture of two 3-octylpyridinium polymers, including 29 and 99 monomeric units, extracted from the Mediterranean sponge, Haliclona (Reniera) sarai, was demonstrated to exert strong specific non-toxic acetylcholinesterase inhibition in vitro. Since first '80s, we found that some tumour types, particular lung tumours present overexpression activity. Acetylcholinesterase is an enzyme associated tothe cholinergic signal system, but also involved cell-tocell communication driving embryonic development regulation several cellular features, such as apoptosis cell movements, cells biopsies. Cytotoxicity tests on immortalized primarycell lines derived (NSCLC) showed poly-APS dose-dependent selective reduction viability, statistically significant. The same cells, exposed salts exhibited loss inthe mitochondrial potential, positive response annexin V assay, T-terminal are markers apoptoticevent. What makes promising anticancer therapy adjuvant they, at concentrations inducing do not affect viability lymphocytes isolated healthy patients. Moreover, three-dimensional cultures (spheroids) exposure show decrease membrane-linked oligosaccharides, responsible for adhesivity metastatic cells. no effects were organs, heart, liver, kidney mice treated by poly-APS, vivo amass density significantly reduced. In this frame, theneed emerges isolation synthetic homologs molecules, order start study therapeutical application drug.

参考文章(51)
Laurent P. Rivory, Jane Hanrahan, Helen M. Dodds, The inhibition of acetylcholinesterase by irinotecan and related camptothecins: key structural properties and experimental variables. Anti-cancer Drug Design. ,vol. 16, pp. 239- 246 ,(2001)
Kristina Sepčić, Nataša Poklar, Gorazd Vesnaver, Didier Fournier, Tom Turk, Peter Maček, Interaction of 3-alkylpyridinium polymers from the sea sponge Reniera sarai with insect acetylcholinesterase. Journal of Protein Chemistry. ,vol. 18, pp. 251- 257 ,(1999) , 10.1023/A:1021096726288
György Hajnóczky, György Csordás, Rajeshwari Krishnamurthy, Gábor Szalai, Mitochondrial calcium signaling driven by the IP3 receptor. Journal of Bioenergetics and Biomembranes. ,vol. 32, pp. 15- 25 ,(2000) , 10.1023/A:1005504210587
Ulrich Drews, Cholinesterase in embryonic development. Progress in Histochemistry and Cytochemistry. ,vol. 7, pp. 1- 52 ,(1975)
I Wessler, C J Kirkpatrick, Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. British Journal of Pharmacology. ,vol. 154, pp. 1558- 1571 ,(2009) , 10.1038/BJP.2008.185
Tom Turk, Kristina Sepčić, Ines Mancini, Graziano Guella, 3-Akylpyridinium and 3-Alkylpyridine Compounds from Marine Sponges, Their Synthesis, Biological Activities and Potential Use Studies in natural products chemistry. ,vol. 35, pp. 355- 397 ,(2008) , 10.1016/S1572-5995(08)80009-9
Maria Grazia Aluigi, Sonya Trombino, Carla Falugi, Lorenzo Gallus, P Piomboni, B Baccetti, S. Stringara, Cristiano Angelini, Acetylcholine synthesis and possible functions during sea urchin development. European Journal of Histochemistry. ,vol. 48, pp. 235- 244 ,(2004) , 10.4081/892
Debra McLaggan, Noppadon Adjimatera, Kristina Sepčić, Marcel Jaspars, DavidJ MacEwan, IanS Blagbrough, RoderickH Scott, Pore forming polyalkylpyridinium salts from marine sponges versus synthetic lipofection systems: distinct tools for intracellular delivery of cDNA and siRNA. BMC Biotechnology. ,vol. 6, pp. 6- 6 ,(2006) , 10.1186/1472-6750-6-6
Frederik B. Thunnissen, Acetylcholine Receptor Pathway and Lung Cancer Journal of Thoracic Oncology. ,vol. 4, pp. 943- 946 ,(2009) , 10.1097/JTO.0B013E3181AD83FC
J. D. Gearhart, B. Mintz, Contact-mediated myogenesis and increased acetylcholinesterase activity in primary cultures of mouse teratocarcinoma cells. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 71, pp. 1734- 1738 ,(1974) , 10.1073/PNAS.71.5.1734