Verbascoside represses malignant phenotypes of esophageal squamous cell carcinoma cells by inhibiting CDC42 via the HMGB1/RAGE axis
Mingming Ji, Jian Sun, Jun Zhao
Abstract
BACKGROUND: As an aggressive human malignancy, esophageal squamous cell carcinoma (ESCC) is prevalent globally, especially in China. Verbascoside (VE) exerts anti-cancer effects in several human cancers. This work was to investigate the effects of VE on ESCC cells. METHODS: Esophageal squamous cell carcinoma cell proliferation, apoptosis, migration, and invasion were assessed by CCK-8, TUNEL, and Transwell assays. Gene and protein levels were detected by RT-qPCR and western blotting. CDC42 activity was evaluated by G-lisa assay. RESULTS: Verbascoside significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in ESCC cells. Furthermore, it was found that VE markedly inhibited HMGB1 and RAGE expression in a dose-dependent manner. Besides, HMGB1/RAGE upregulation partially reversed the anti-cancer effects of VE on ESCC cells. VE repressed HMGB1/RAGE-induced CDC42 activation in ESCC cells. In addition, ML141-mediated CDC42 inactivation further enhanced the effect of VE on ESCC cell proliferation, apoptosis, migration, and invasion. CONCLUSIONS: Our findings indicated that VE has significant anti-tumor potential in ESCC by suppressing HMGB1/RAGE-dependent CDC42 activation.