Natural triterpenoid saponin Momordin Ic suppresses HepG2 cell invasion via COX-2 inhibition and PPARγ activation.

We previously reported that Momordin Ic, a natural triterpenoid saponin from the fruit of Kochia scoparia (L.) Schrad., exerts good anti-invasive activity on liver cancer partly by altering E-cadherin, VCAM-1, ICAM-1 and MMP-9. The JNK and p38-MAPK pathways differentially altered the four molecules to some extent. However, MMP-9, which is greatly suppressed by Momordin Ic, was affected by neither p38-MAPK nor JNK. Therefore, we further investigated how other signals previously found to regulate cell growth, such as COX-2 and PPARγ, function in the process of cell invasion by western blot. The results demonstrated that COX-2 and PPARγ play a significant role in Momordin Ic-inhibited cell invasion. However, COX-2 only regulated E-cadherin and ICAM-1. PPARγ was not involved in VCAM-1alteration but was significant for the expressions of other proteins. Akt, a kinase upstream of COX-2 and PPARγ, did not influence ICAM-1 but directly mediated the expression of E-cadherin, VCAM-1 and MMP-9. Momordin Ic weakens HepG2 cell invasion through PPARγ activation and COX-2 inhibition. These findings provide evidence for the anti-invasion mechanism of Momordin Ic.