Solanum lyratum-Derived Solalyraine A1 Suppresses Non-Small Cell Lung Cancer Through Regulation of Exosome Secretion and Related Protein Biomarkers

<b>Background</b>: Lung cancer is a prevalent malignancy globally, with non-small cell lung cancer (NSCLC) accounting for 80-85% of cases. Solalyraine A1 (SA1) is a steroidal glycoalkaloid derived from <i>Solanum lyratum</i>. However, the effect and mechanism of SA1 on NSCLC remain unclear. <b>Methods</b>: The exosomes from SA1-treated A549 cells were prepared and administered to A549 xenograft mice. Proteomics analysis of SA1-treated A549 cells and their exosomes was conducted to assess the mechanism. Bioinformatics analysis was utilized to identify differentially expressed proteins (DEPs) and key signaling pathways. Western blot analysis confirmed the expression of potential targets. <b>Results</b>: SA1 effectively suppressed tumor growth in A549 xenografts, demonstrating a remarkable inhibition rate of 70.48%. A total of 1154 DEPs were identified in A549 cells, primarily associated with the ribosome pathway. Additionally, 746 DEPs were identified in exosomes, mainly involved in the spliceosome pathway. Five highly regulated DEPs were selected for verification. SA1 was found to suppress MUC5B and elevate APOB expression in A549 cells, while inhibiting MFGM, ANGL4 and increasing GCN1 expression in exosomes. <b>Conclusions</b>: This study demonstrates that SA1 exhibits anti-NSCLC effects by regulating exosome function and related protein expression, providing novel insights for NSCLC treatment.