APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma

Zovko, Ana (author), Viktorsson, Kristina (author), Lewensohn, Rolf (author), Kološa, Katja (author), Filipič, Metka (author), Xing, Hong (author), Kem, William R. (author), Paleari, Laura (author), Turk, Tom (author)

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.

• Language: English
• Keywords: 3-alkylpyridinium polymers, apoptosis, nicotine, nicotinic acetylcholine receptor, non-small cell lung carcinoma
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2013
• Number of pages: Str. 2574-2594
• Numbering: Vol. 11, iss. 7
• PID: 20.500.12556/RUL-37728
• UDC: 577.1
• ISSN on article: 1660-3397
• DOI: 10.3390/md11072574
• COBISS.SI-ID: 2854223
• Publication date in RUL: 10.07.2015

Record is a part of a journal

• Title: Marine drugs
• Shortened title: Mar. drugs
• Publisher: MDPI
• ISSN: 1660-3397
• COBISS.SI-ID: 23578841

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• Licensing start date: 16.07.2013