Veratramine Inhibits Human Non-Small Cell Lung Cancer Cell Growth by Inhibiting the Hedgehog Signaling Pathway

Objectives: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in both males and females. Considering the growing impact of NSCLC on public health, there is an urgent need for additional treatment strategies. Veratramine, a natural steroidal alkaloid extracted from the roots of plants in the lily family, has recently garnered attention regarding its potential anti-cancer effects. However, to the best of our knowledge, the role of veratramine in the progression of lung cancer is unclear. Methods: The various concentration of veratramine were applied to the NSCLC cell lines (A549, NCI-H358 and NCI-H1299). The cell viability, apoptosis, and the cell cycle were evaluated using CCK-8 and flow cytometry assays. Phenotype of NSCLC cells were examined using an optical microscope and ImageJ software. Protein expression in veratramine-treated NSCLC cells was measured using immunoblotting. Results: Veratramine-treated NSCLC cells exhibited significantly reduced cell viability and migration ability. Flow cytometry (i.e., fluorescence-activated cell sorting) revealed that treatment with veratramine increased apoptosis and cell cycle delay. Immunoblotting indicated that the Hedgehog (Hh) signaling pathway was significantly downregulated via inhibiting gli1 expression. Cell cycle-related proteins in NSCLC cells were decreased by veratramine treatment. Conclusion: Veratramine suppresses lung cancer cell growth by inhibiting the Hh signaling pathway, suggesting its potential applicability in the treatment of NSCLC.