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

## TL;DR

Saucerneol, a compound from Saururus chinensis, inhibits osteosarcoma cell growth and prevents bone degradation in lab models.

## Contribution

Saucerneol's anti-osteosarcoma effects via JAK2/STAT3 inhibition and mitochondrial disruption are newly demonstrated.

## Key findings

- Saucerneol induces apoptosis in osteosarcoma cells by disrupting mitochondrial function and increasing ROS.
- Saucerneol inhibits cell migration, invasion, and anchorage-independent growth in osteosarcoma models.
- Saucerneol reduces metastasis-associated osteolysis in ex vivo bone cultures.

## Abstract

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.

Saucerneol (Sauc) is a phytochemical compound classified as a lignan, derived from Saururus chinensis. The JAK2/STAT3 signaling pathway is the primary target of Sauc in osteosarcoma cells. Sauc disrupts mitochondrial potential and increases reactive oxygen species (ROS), leading to apoptotic cell death. Sauc attenuates metastasis‐associated osteolysis in ex vivo bone organ cultures. Sauc may serve as promising a daily health supplement and phytomedicine.