Wogonin suppresses the LPS-enhanced invasiveness of MDA-MB-231 breast cancer cells by inhibiting the 5-LO/BLT2 cascade

Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)-enhanced invasiveness of MDA-MB-231 cells. In addition, wogonin inhibited the synthesis of interleukin-8 (IL-8) and matrix metallopeptidase-9 (MMP-9), which are critical for promoting invasiveness in MDA-MB-231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5-lipoxygenase (5-LO) in LPS-stimulated MDA-MB-231 cells. Notably, wogonin attenuated the production of IL-8 and MMP-9 by inhibiting the BLT2/extra-cellular signal-regulated kinase (ERK)-linked cascade. Finally, in vivo, LPS-driven MDA-MB-231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5-LO/BLT2/ERK/IL-8/MMP-9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.