Esculentoside H inhibits colon cancer cell migration and growth through suppression of MMP‐9 gene expression via NF‐kB signaling pathway

Abstract A water‐soluble saponin, Esculentoside H (EsH), 3‐ O ‐( O ‐β‐ d ‐glucopyranosyl‐(1→4)‐β‐ d ‐xylopyranosyl)‐28‐β‐ d ‐glucopyranosylphytolaccagenin has been isolated and purified from the root extract of perennial plant Phytolacca esculenta . EsH is known to be an anticancer compound, having a capacity for TNF‐α release. However, the effects of EsH on migration and growth in tumor cells have not yet been reported. In the current study, the suppressive effects of EsH on phorbol 12‐myristate 13‐acetate (PMA)‐induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. Interestingly, the transwell assay and wound healing show that EsH suppresses the PMA‐induced migration and growth potential of HCT116 and CT26 colon cancer cells, respectively. EsH dose‐dependently suppressed matrix metalloproteinases‐9 (MMP‐9) expression that was upregulated upon PMA treatment in messenger RNA levels and protein secretion. Since the expression of MMP‐9 is correlated with nuclear factor‐κB (NF‐κB) signaling, it has been examined whether EsH inhibits PMA‐induced IκB phosphorylation that leads to the suppression of NK‐κB nuclear translocation. EsH repressed the phosphorylation level of JNK, but not extracellular signal‐regulated kinase and p38 signaling when the cells were treated with PMA. Overall, these results demonstrated that EsH could suppress cancer migration through blockage of the JNK1/2 and NF‐κB signaling‐mediated MMP‐9 expression.