Solasodine suppresses nasopharyngeal carcinoma progression by inducing ferroptosis.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high prevalence in China. Solasodine is a natural compound derived from the traditional herb that possess anticancer activity in various tumors, but its role in NPC remains unclear. Here, we demonstrated that solasodine potently suppressed NPC growth and induced cell death both in vitro and in vivo. Network pharmacology identified HMOX1 as a pivotal target of solasodine linked to ferroptosis. Solasodine triggered ferroptotic hallmarks, including mitochondrial cristae disruption, elevated Fe(2)(+)/ROS/MDA, depleted GSH, and dysregulated ferroptosis-related proteins (HMOX1/COX2 upward arrow, GPX4/MUC1/SLC40A1 downward arrow). Crucially, ferroptosis inhibitors (Fer-1/Lip-1), but not apoptosis, necroptosis, or autophagy inhibitors, rescued solasodine-induced cell death, confirming ferroptosis as the dominant mechanism. In conclusion, by applying network pharmacology accompanied with experimental validation, our study unveils solasodine as a novel ferroptosis inducer for NPC treatment. However, its therapeutic potential requires further validation in patient-derived models and clinical trials.