Santalol Suppresses Lung Metastasis of Colorectal Cancer Cells by Increasing ROS Levels

Santalol (STL), a sesquiterpene alcohol extracted from sandalwood oil, has reported antioxidant, anti-inflammatory, and anticancer effects. Nevertheless, the influence of this compound on lung metastasis of colorectal cancer (CRC) cells has not been insufficiently elucidated. In this study, we investigated the anticancer activity of STL in metastatic CRC cells. STL significantly reduced cell viability and clonogenic capacity in a dose-dependent manner. This compound induced mitochondria-mediated apoptosis of CRC cells by regulating caspases and PARP. In addition, it reduced total antioxidant capacity and increased reactive oxygen species (ROS) levels. These results indicate that STL can enhance mitochondrial depolarization and activate the mitochondrial apoptotic pathway. Using an in vivo murine model, we further demonstrated that STL restricted the pulmonary dissemination of CRC cells. Taken together, these findings reveal that STL hinders lung metastasis of CRC cells via the induction of apoptosis and mitochondrial dysfunction driven by intracellular ROS accumulation. Our findings support STL as a promising therapeutic candidate for metastatic CRC.