“This study gives us important insights into how the lysosomotropic property of nicotine can interfere with the cell’s ability to clean and recycle cellular components — even at concentrations below those found in smoke-free tobacco such as snus. That’s highly relevant when assessing long-term effects on oral tissues,” says PhD candidate Solveig Uvsløkk at NIOM.
What is this about?
In collaboration with other NIOM researchers, as well as researchers from Oulu University Hospital, the University of Oulu, and the Norwegian Institute of Public Health, Uvsløkk has explored a non-receptor-mediated effect of nicotine on lysosomes—the cell's compartment for degradation and recycling—in cultured human tongue epithelial cells (PE/CA-PJ49). While nicotine is known for receptor-mediated actions, this research focused on its direct impact on lysosomal activity and lysosomal degradation pathways. The goal was to understand how nicotine affects key cellular functions, such as autophagy, phagocytosis, and endocytosis.
What did the researchers find out?
Exposure to nicotine alone did not reduce cell viability. However, vacuolization - a form of cellular compartment swelling - occurred rapidly with nicotine exposure. All nicotine-treated cells reduced the lysosomal activity in the cells, similar to the effect of bafilomycin A1, a known inhibitor of lysosomal function. Additionally, levels of autophagy-related proteins p62/SQSTM1 and LC3‑II increased, indicating disrupted autophagic flux and lysosomal dysfunction.
Key results from the project
- Nicotine induced cell vacuolization
- Lysosomal activity was consistently reduced in all exposure scenarios
- Increases in p62/SQSTM1 and LC3‑II suggest impaired autophagy, meaning the cells struggled with clearing or recycling damaged components
These findings highlight that nicotine can affect cellular degradation pathways in tongue epithelial cells by a mechanism different from the well-known receptor-mediated effects. Such disruptions may have implications for oral health and the ability of cells to handle other toxic exposures. This is particularly relevant in the context of nicotine exposure from snus or tobacco-free nicotine pouches.