Suppressive effects of Momordin Ic on HepG2 cell migration and invasion by regulating MMP-9 and adhesion molecules: Involvement of p38 and JNK pathways.

Momordin Ic was previously found to induce liver cancer cell apoptosis and autophagy. To further elucidate the anti-cancer activity of Momordin Ic, we analyzed the suppressive effects of Momordin Ic on cell migration and invasion. We also investigated the mechanisms associated with MMP-9, adhesion molecules and signaling transductions. The results demonstrated that Momordin Ic effectively prevented cell attachment, migration and invasion. E-cadherin, mediation of homotypic adhesion was induced while VCAM-1 and ICAM-1 and MMP-9 were inhibited. Momordin Ic influenced phosphorylations of p38, JNK and Erk with VEGF. p38 effectively regulated expressions of E-cadherin, VCAM-1 and ICAM-1. JNK greatly contributed to E-cadherin alteration. Erk hardly modified E-cadherin, VCAM-1, ICAM-1 and MMP-9 although Erk phosphorylation decreased by Momordin Ic. These results revealed Momordin Ic prevent cell invasion by inhibiting VCAM-1, ICAM-1, MMP-9 but inducing E-cadherin expression via p38 and JNK pathways. Thus momordin Ic may be a promising candidate with anti-cancer bioactivity.