Stearoyl-CoA Desaturase-1 (SCD1) inhibition as a potential therapeutic strategy for targeting lung cancer stem cells

Lung cancer stem cells (CSCs) are highly resistant to current therapy methods, which leads to a high likelihood of cancer relapse. The aim of this study was to investigate whether the enzyme Stearoyl-CoA Desaturase-1 (SCD1) plays a role in mediating the reactive oxygen species (ROS) resistance in CSCs derived from the A549 lung adenocarcinoma cell line. In our experiments, CSCs were cultured, and their stem cell identity was confirmed via marker analysis. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were quantified using liquid chromatography–mass spectrometry (LC-MS). SCD1 expression was assessed through quantitative real-time PCR analysis and western blotting. Our results showed that CSCs expressed significantly higher levels of MUFAs and SCD1 in comparison to bulk A549 cells. Based on these findings, we employed SCD1 inhibitors in the medicinal assay. We found increased CSCs death following treatment with SCD1 inhibitors in combination with ROS inducers (Tert-butyl hydroperoxide and hydrogen peroxide). These findings suggest that SCD1 contributes to ROS resistance and cell survival in lung cancer and indicate that targeting SCD1 could potentially be used as a therapeutic method to enhance ROS-based cancer treatments. Further studies could investigate SCD1’s role in vivo and its potential in combination with other treatment methods.