title: APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma.
abstract: Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer.
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia. ana.zovko@ki.se
authors.forename: Ana
authors.initials: A
authors.lastname: Zovko
authors.forename: Kristina
authors.initials: K
authors.lastname: Viktorsson
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Katja
authors.initials: K
authors.lastname: Kološa
authors.forename: Metka
authors.initials: M
authors.lastname: Filipič
authors.forename: Hong
authors.initials: H
authors.lastname: Xing
authors.forename: William R
authors.initials: WR
authors.lastname: Kem
authors.forename: Laura
authors.initials: L
authors.lastname: Paleari
authors.forename: Tom
authors.initials: T
authors.lastname: Turk
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001685:Biological Factors / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry; D011726:Pyridinium Compounds / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001685:Biological Factors; D011108:Polymers; D011726:Pyridinium Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor; C115254:poly-APS; D000110:Acetylcholinesterase; D053453:Caspase 9