Attenuation of Nicotine Effects on A549 Lung Cancer Cells by Synthetic α7 nAChR Antagonists APS7-2 and APS8-2

Joukhan, Ahmad (author), Kononenko, Veno (author), Bele, Tadeja (author), Sollner Dolenc, Marija (author), Peigneur, Steve (author), Lopes Pinheiro-Junior, Ernesto (author), Tytgat, Jan (author), Turk, Tom (author), Križaj, Igor (author), Drobne, Damjana (author)

Nicotine binds to nicotinic acetylcholine receptors (nAChRs) that are overexpressed in different cancer cells, promoting tumor growth and resistance to chemotherapy. In this study, we aimed to investigate the potential of APS7-2 and APS8-2, synthetic analogs of a marine sponge toxin, to inhibit nicotine-mediated effects on A549 human lung cancer cells. Our electrophysiological measurements confirmed that APS7-2 and APS8-2 act as α7 nAChR antagonists. APS8-2 showed no cytotoxicity in A549 cells, while APS7-2 showed concentration-dependent cytotoxicity in A549 cells. The different cytotoxic responses of APS7-2 and APS8-2 emphasize the importance of the chemical structure in determining their cytotoxicity on cancer cells. Nicotine-mediated effects include increased cell viability and proliferation, elevated intracellular calcium levels, and reduced cisplatin-induced cytotoxicity and reactive oxygen species production (ROS) in A549 cells. These effects of nicotine were effectively attenuated by APS8-2, whereas APS7-2 was less effective. Our results suggest that APS8-2 is a promising new therapeutic agent in the chemotherapy of lung cancer.

• Language: English
• Keywords: marine toxin, nicotinic acetylcholine receptor, nAChR antagonist, APS7-2, APS8-2
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 14 str.
• Numbering: Vol. 22, iss. 4
• PID: 20.500.12556/RUL-155641
• UDC: 615.9:616.24-006
• ISSN on article: 1660-3397
• DOI: 10.3390/md22040147
• COBISS.SI-ID: 190758147
• Publication date in RUL: 09.04.2024

Record is a part of a journal

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

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: rak (medicina), toksičnost, morski toksini, nikotinski acetilholinski receptor, antagonist nAChR, APS7-2, APS8-2