Induction of A549 Nonsmall‐Cell Lung Cancer Cells Proliferation by Photoreleased Nicotine

Caged compounds comprise the group of artificially synthesized, light‐sensitive molecules that enable in situ derivation of biologically active constituents capable of affecting cells, tissues and/or biological processes upon exposure to light. Ruthenium‐bispyridine (RuBi) complexes are photolyzed by biologically harmless visible light. In the present study, we show that RuBi‐caged nicotine can be used as a source of free nicotine to induce proliferation of A549 nonsmall‐cell lung cancer (NSCLC) cells by acting on nicotinic acetylcholine receptors expressed in these cells. RuBi‐nicotine was photolyzed using LED light source with the spectrum matching RuBi‐absorption. Photorelease of free nicotine ([Nic]p/r) was quantified by high‐performance liquid chromatography (HPLC). 5‐s‐long light exposure of 10 μm of RuBi‐nicotine generated 2 μm [Nic]p/r which enhanced A549 cell proliferation similarly to the 2 μm of plain nicotine during 72 h of cell culturing. Both RuBi‐nicotine per se and its photolysis byproduct exerted no effect on A549 cells. We conclude that RuBi‐nicotine can be a good source of free nicotine for inducing short‐ and long‐term biological effects. Photolysis of RuBi‐nicotine is quite effective, and can produce biologically relevant concentrations of nicotine at acceptable concentrations of the source material with the use of simple, inexpensive, and easily accessible light sources.

[1]  Indrajeet Patil,et al.  Visualizations with statistical details: The 'ggstatsplot' approach , 2021, J. Open Source Softw..

[2]  Yevgenia Kozorovitskiy,et al.  Photoactivatable drugs for nicotinic optopharmacology , 2018, Nature Methods.

[3]  Hai-ji Sun,et al.  Alpha5 Nicotinic Acetylcholine Receptor Contributes to Nicotine-Induced Lung Cancer Development and Progression , 2017, Front. Pharmacol..

[4]  Kira E. Poskanzer,et al.  A Visible-Light-Sensitive Caged Serotonin. , 2017, ACS chemical neuroscience.

[5]  S. Grando,et al.  Connections of nicotine to cancer , 2014, Nature Reviews Cancer.

[6]  S. Chellappan,et al.  Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers , 2014, Molecular Cancer Research.

[7]  R. Etchenique,et al.  Ruthenium polypyridyl phototriggers: from beginnings to perspectives , 2013, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[8]  R. Etchenique,et al.  A caged nicotine with nanosecond range kinetics and visible light sensitivity. , 2010, Journal of inorganic biochemistry.

[9]  P. Dasgupta,et al.  Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis. , 2008, Trends in pharmacological sciences.

[10]  G. Ellis‐Davies,et al.  Caged compounds: photorelease technology for control of cellular chemistry and physiology , 2007, Nature Methods.

[11]  K. Audus,et al.  Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. , 1998, Experimental cell research.

[12]  M A Russell,et al.  Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. , 1980, British medical journal.

[13]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[14]  Roberto Etchenique,et al.  A new strategy for neurochemical photodelivery: metal-ligand heterolytic cleavage. , 2003, Journal of the American Chemical Society.

[15]  J. R. Scotti,et al.  Available From , 1973 .