Engeletin suppresses cervical carcinogenesis in vitro and in vivo by reducing NF-κB-dependent signaling

Cervical cancer is an aggressive human cancer with poor prognosis among women, and urgently requires effective treatments. Engeletin (ENG, dihydrokaempferol 3-rhamnoside), as a flavanonol glycoside, could be found in various kinds of vegetables and fruits, exerting significant anti-inflammatory biological activities. However, its role in regulating cervical cancer, as well as the underlying molecular mechanisms are still unknown. In this study, we found that ENG treatments dose-dependently reduced the proliferation of cervical cancer cells. Epithelial to mesenchymal transition (EMT) process in cervical cancer was also restrained by ENG using transwell analysis, as evidenced by the significantly reduced migration and invasion. In addition, ENG treatments restricted vascular endothelial growth factor-A (VEGFA) expression in cervical cancer cells, contributing to the suppression of angiogenesis. Mechanistically, ENG significantly reduced the expression of chemokine (C-C motif) ligand 2 (CCL2) in cervical cancer cells associated with the blockage of nuclear factor-κB (NF-κB) signaling pathway. Moreover, ENG functioned as an inhibitor of NF-κB, which was involved in the repression of angiogenesis. In xenograft model, ENG treatment effectively reduced the tumor volume and weight, accompanied with decreased expression of phosphorylated NF-κB, CCL2 and VEGFA, and showed little influence on the body weight change. Therefore, ENG might be a potential therapeutic strategy for the treatment of cervical cancer.