Abstract
Evodiamine (EVO) is one of the main components extracted from Evodia rutaecarpa and has been reported to inhibit tumor growth by inhibiting proliferation and inducing apoptosis. Although the anticancer activity of evodiamine has been confirmed, the exact mechanism remains to be elucidated. In the present study, cancer stem-like cells (CSCs) were successfully enriched from A549 cells by being cultured in serum-free medium and characterized by detecting stemness markers. Expectedly, the addition of EVO inhibited proliferation, migration and invasion in A549 cells, demonstrating its inhibitory effects on the malignant behaviors of A549 cells. In CSCs derived from A549 cells, EVO treatment promoted cell proliferation while inhibiting migration and invasion. By detecting the hallmarks of the epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Slug and Snail via western blotting, it was revealed that EVO treatment inactivated the EMT process and potentially led to the loss of self-renewal capacity of CSCs and promoted proliferation. By activating the EMT using TGF-β pretreatment, EVO treatment downregulated the hallmarks of the EMT and led to inactivation of the EMT, indicating its potential mechanism of regulating CSCs via the EMT pathway. The findings suggested that modulation of the self-renewal capacity of CSCs may affect malignant cancer behaviors following surgery. EVO exerts inhibitory effects not only on cancer cells but also on CSCs in non-small-cell lung cancer, and therefore could be used as a promising drug targeting CSCs.