This study responds to the pressing need for novel therapeutic strategies to address key challenges in non-small cell lung cancer (NSCLC) treatment. It explores effective traditional Chinese medicine, investigates its molecular mechanism, and pursues the modernization of traditional Chinese medicine. The current research investigated how Solasonine (SS) extracted from Solanum nigrum L. may counter NSCLC by activating the ferroptosis pathway, while also elucidating the fundamental molecular mechanisms involved. Proliferation (CCK8) and metastasis (wound healing) of A549/HCC1833 cells were assessed. Reactive oxygen species (ROS) production, proteomic sequencing, co-immunoprecipitation (Co-IP), and molecular docking mechanisms of the SS treatment group were analyzed. SLC7A11 regulation was evaluated using ferroptosis inhibitors and by ubiquitination assays. SS efficacy was tested in a subcutaneous/lung metastasis nude mouse model. SS suppressed NSCLC proliferation/metastasis by inducing ferroptosis. Proteomics revealed SS downregulated ferroptosis-related proteins and SLC7A11. SS promoted SLC7A11 ubiquitination/degradation via USP10/TRIM25 interactions, confirmed by Co-IP/docking. In vitro/vivo, SS increased ROS, inhibited tumor growth/metastasis, and activated ferroptosis pathways (reduced SLC7A11/GPX4/GSR/GSS). Immunohistochemistry confirmed the presence of ferroptosis markers in tumors. SS triggers ferroptosis in NSCLC by disrupting USP10/TRIM25-mediated SLC7A11 stability. This study proposes a novel treatment strategy for NSCLC with a traditional Chinese medicine monomer. The graphical abstract of the present study. Solasonine, as one of the most important components of Solanum nigrum L., competitively binds to SLC7A11 with the deubiquitinating enzyme USP10, thereby promoting TRIM25 to bind to SLC7A11 and causes SLC7A11 to be ubiquitinated and degraded by TRIM25, stimulating ROS production and causing ferroptosis to inhibit the malignant progression of NSCLC. 1. Solasonine inhibits non-small cell lung cancer (NSCLC) growth and spread by triggering a specific cell death form termed ferroptosis. 2. This anti-cancer effect involves Solasonine reducing levels of the key protein SLC7A11 and enhancing its degradation through ubiquitination. 3. The novel molecular mechanism reveals that Solasonine promotes SLC7A11 ubiquitination via the USP10/TRIM25 regulatory axis, thereby targeting ferroptosis pathways in NSCLC.
Wang et al. (Wed,) studied this question.