Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells.
J Agric Food Chem. 2018 Jul 9. Epub 2018 Jul 9. PMID: 29945448
The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.