APS8, a Polymeric Alkylpyridinium Salt Blocks alpha 7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

作者：Zovko Ana; Viktorsson Kristina; Lewensohn Rolf; Kolosa Katja; Filipic Metka; Xing Hong; Kem William R; Paleari Laura; Turk Tom^*

来源：Marine Drugs, 2013, 11(7): 2574-2594.

DOI：10.3390/md11072574

• 3-alkylpyridinium polymers
• apoptosis
• nicotine
• nicotinic acetylcholine receptor
• non-small cell lung carcinoma

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 7 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.

• 出版日期2013-7