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

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2024 Apr 26

PMID 38667764

Authors

Ahmad Joukhan

Veno Kononenko

Tadeja Bele

Marija Sollner Dolenc

Steve Peigneur

Ernesto Lopes Pinheiro-Junior

Jan Tytgat

Tom Turk

Igor Krizaj

Damjana Drobne

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Modulation of the Effect of Cisplatin on Nicotine-Stimulated A549 Lung Cancer Cells Using Analog of Marine Sponge Toxin Loaded in Gelatin Nanoparticles.

Joukhan A, Kononenko V, Dolenc M, Hocevar M, Turk T, Drobne D Nanomaterials (Basel). 2024; 14(9).

PMID: 38727371 PMC: 11085658. DOI: 10.3390/nano14090777.

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