The root bark of Morus alba L. (MA) has been traditionally used for the treatment of various lung diseases in Korea. Although recent research has demonstrated its anticancer effects in several cancer cells, it is still unclear whether MA inhibits the migratory ability of lung cancer cells. The present study investigated the effects of MA on the migration of lung cancer cells and explored the underlying mechanism. Results from a transwell assay and wound-healing assay demonstrated that methylene chloride extracts of MA (MEMA) suppressed the migration and invasion of H1299, H460, and A549 human non-small-cell lung cancer (NSCLC) cells in a concentration-dependent manner. Results from Western blot analyses showed that MEMA reduced the phosphorylation of STAT3 and Src. In addition, MEMA downregulated the expression of epithelial-mesenchymal transition (EMT) marker proteins including Slug, Snail, Vimentin, and N-cadherin, while upregulating the expression of Occludin-a tight-junction protein. The regulation of EMT markers and the decrease of migration by MEMA treatment were reversed once phospho-mimetic STAT3 (Y705D) or Src (Y527F) was transfected into H1299 cells. In conclusions, MEMA inhibited the migratory activity of human NSCLC cells through blocking Src/STAT3-mediated EMT.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is a major obstacle in managing lung cancer. The root of Scutellaria baicalensis (SB) traditionally used for fever clearance and detoxification possesses various bioactivities including anticancer effects. The purpose of this study was to investigate whether SB exhibited anticancer activity in EGFR TKI-resistant lung cancer cells and to explore the underlying mechanism. We used four types of human lung cancer cell lines, including H1299 (EGFR wildtype; EGFR TKI-resistant), H1975 (acquired TKI-resistant), PC9/ER (acquired erlotinib-resistant), and PC9/GR (acquired gefitinib-resistant) cells. The ethanol extract of SB (ESB) decreased cell viability and suppressed colony formation in the four cell lines. ESB stimulated nuclear fragmentation and the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3. Consistently, the proportion of sub-G1 phase cells and annexin V+ cells were significantly elevated by ESB, indicating that ESB induced apoptotic cell death in EGFR TKI-resistant cells. ESB dephosphorylated signal transducer and activator of transcription 3 (STAT3) and downregulated the target gene expression. The overexpression of constitutively active STAT3 reversed ESB-induced apoptosis, suggesting that ESB triggered apoptosis in EGFR TKI-resistant cells by inactivating STAT3. Taken together, we propose the potential use of SB as a novel therapeutic for lung cancer patients with EGFR TKI resistance.