Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis
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Updated: Jan 30, 2026

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
Published on: May 24, 2014
Yuhan Wang1,2, Xiaodan Li1,3, Chuanqiang Zhou1
1Shanghai Key Laboratory of Molecular Imaging, Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
Abstract:
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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