Sweet apple e-cigarette vapor differentially modulates the mTOR pathway in oral squamous cell carcinoma cell lines

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and is associated with high recurrence and poor prognosis. This study investigated the effects of Sweet Apple e-cigarette vapor extract (Apple EVE), with and without nicotine, on mTOR pathway activation in OSCC cell lines Ca9-22 and Cal 27.

Cells were exposed for 6 hours to 10% Apple EVE generated from "Reds Apple Juice" in the presence or absence of nicotine (6 mg), with untreated cells as controls. Phosphorylation levels of mTOR pathway components (p-mTOR, p-p70S6K, p-4EBP1, and p-AKT) were assessed by Western blot and quantified by densitometry normalized to β-actin. Cell invasion was evaluated using a Matrigel-coated real-time xCELLigence assay. Data were analyzed using the Mann-Whitney U test (p < 0.05).

Nicotine-containing Apple EVE significantly increased p-mTOR in both cell lines. In Ca9-22 cells, it decreased p-p70S6K and p-4EBP1, whereas in Cal 27 cells it increased p-AKT. Apple EVE without nicotine induced more modest and variable effects. No significant changes in cell invasion were observed in either cell line.

Apple EVE, particularly when combined with nicotine, differentially modulates mTOR signaling in a cell line-specific manner in OSCC cells. These findings highlight the complex effects of flavored e-cigarette aerosols on cancer-related pathways and warrant further investigation into the functional consequences of these early signaling changes.