Hinokitiol reduces tumor metastasis by regulating epithelial cell adhesion molecule via protein kinase-B/mammalian target of rapamycin signaling pathway.

Tumor metastasis is the leading cause of death in cancer patients. Epithelial cell adhesion molecule (EpCAM) is abundantly expressed in various malignant tumors and plays a crucial role in cell adhesion, metastasis, proliferation, and differentiation. This study investigated the effects of hinokitiol, a natural tropolone compound known for its antiviral, anti-inflammatory, and antibacterial properties, on tumor growth and metastasis. Specifically, the study focused on the expression of EpCAM in mouse tumor cells treated with hinokitiol. Hinokitiol was administered to mouse melanoma cells (B16F10) and mouse colorectal carcinoma cells (CT26), resulting in a significant decrease in EpCAM expression. Additionally, the protein levels involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway were reduced following hinokitiol treatment. Using wound healing and Transwell assays, the study demonstrated that hinokitiol effectively inhibits cancer cell migration. In vivo experiments were conducted using mice, which were injected intravenously with B16F10 or CT26 cells to induce tumor metastasis. The tumor cells were either treated with hinokitiol or left untreated. The results showed that tumor cells treated with hinokitiol exhibited significantly reduced tumor size and weight in the lungs, as well as prolonged survival, compared to untreated tumor cells. This study concludes that hinokitiol inhibits tumor migration by downregulating EpCAM via the AKT/mTOR signaling pathway and exhibits positive effects in vivo.