Liquiritigenin inhibits the migration, invasion, and EMT of prostate cancer through activating ER stress
Chi Wang, Bo Liu, Weichao Dan, Yi Wei, Mengxing Li, Chendong Guo, Yishuai Zhang, Hongjun Xie
Abstract
Liquiritigenin (LQ) is a monomeric compound found in licorice, a leguminous plant, and has been reported to exhibit antitumor effects in various lines of cancer cells. However, the underlying molecular mechanisms by which LQ exerts its antitumor effects remain largely unknown. In this study, the effects of LQ on the migration, invasion, and epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells were investigated. We found that LQ effectively inhibited the migration and invasion of PCa cells in vitro, and this effect was further confirmed in xenograft lung metastasis models. In addition, LQ was found to activate endoplasmic reticulum stress (ER stress) in PCa cells. Further studies found that LQ upregulated the expression of inositol-requiring enzyme type 1α (IRE1). When IRE1 was knocked down, we observed a weakened inhibitory effect of LQ treatment on the migration and invasion of PCa cells. This observation suggests that LQ may inhibit the migration, invasion and EMT of PCa cells through activating the IRE1 branch of ER stress. In conclusion, our research may provide a novel therapeutic strategy for PCa. • LQ inhibits the metastasis and epithelial-mesenchymal transition (EMT) of PCa cells. • LQ induces ER stress in PCa cells and promotes the expression levels of IRE1. • LQ inhibits the metastasis and EMT of PCa via activation of the IRE1 branch of ER stress. • LQ inhibits the proliferation of subcutaneous transplanted tumors and the colonization of lung metastases in mice. • LQ might serve as an effective agent for PCa treatment.