The effectiveness of sanggenon c in alleviating SLC7A11-induced ferroptosis in lung cancer was evaluated using in vivo, in vitro, and computational approaches.

Sanggenon c, a component in Morus alba L, has been proved to possess various biological activities. The aim of this study is to investigate whether sanggenon c can target SLC7A11 and inhibit lung cancer by regulating the ferroptosis mechanism. The levels of antioxidant factor, Fe , and SLC7A11 were measured in the lungs of cancerous mice and human A 549 lung cancer cells. The computer-aided techniques were employed to validate the molecular docking and molecular dynamics simulations of sanggenon c and SLC7A11. The sanggenon c significantly inhibits lung cancer cell metastasis in vivo and A 549 cell proliferation in vitro by targeting the over-expression of SLC7A11, which inhibits GPX 4 and induces the release of ROS and MDA, effectively triggering ferroptosis. The interaction between sanggenon c and SLC7A11 exhibits a strong binding affinity, leading to the significant inhibition of the key protein SLC7A11. This restriction of system xc- transport induces ferroptosis in lung cancer. It epitomizes a groundbreaking inhibitor specifically designed to target SLC7A11.