Saucerneol Inhibits the Growth, Migration, and Invasion of Osteosarcoma Cells In Vitro and Prevents Metastasis‐Associated Osteolysis Ex Vivo

Saururus chinensis has traditionally been used to treat various diseases. Biologically active compounds isolated from S. chinensis exhibit diverse pharmacological activities. The aim of this study was to investigate the antiosteosarcoma effects of saucerneol (Sauc), a lignan, purified from the aerial parts of S. chinensis using in vitro and ex vivo experimental models. Sauc was purified from the methanolic extract of S. chinensis. It exhibited toxicity against MG63 and SJSA-1 cells (human osteosarcoma cell lines), inducing apoptotic morphological changes and suppressing cell migration. Sauc triggered PARP cleavage and decreased the expression of antiapoptotic proteins. It also disrupted mitochondrial membrane potential and increased reactive oxygen species (ROS) generation. Proteome profiling, western blotting, and immunocytochemistry revealed that Sauc inhibited the JAK2/STAT3 pathway. Furthermore, Sauc downregulated the expression of metastasis-associated proteins, suppressed invasion through extracellular matrix-coated membranes, and inhibited anchorage-independent cell growth. In an ex vivo bone organ culture, Sauc attenuated tumor-induced osteolysis. This study demonstrated that Sauc exerts anti-osteosarcoma effects by inducing apoptosis, inhibiting cell migration and invasion in vitro, and mitigating metastasis-associated bone degradation ex vivo. Thus, Sauc holds promise as a protective compound in daily health supplements and a therapeutic agent against human osteosarcoma.