Inhibitory effects of GL-V9 on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-2/9

Abstract: Cancer cell invasion plays a crucial role in growth and local spreading of tumors. GL-V9 is a newly synthesized flavonoid that has been shown to possess an antitumor effect. However, the mechanism of GL-V9 in preventing tumor growth is still unclear. The purpose of this study is to investigate the anti-invasive and anti-metastatic activity of this novel compound in MDA-MB-231 and MCF-7 human breast carcinoma cells. In this study, GL-V9 caused a concentration-dependent suppression of cell adhesive ability by cell adhesion assay, it also inhibited the migration and invasion of cells by wound healing assay and transwell invasion assay in a concentration-dependent manner. Considering matrix metalloproteinases (MMPs) play an important role in metastatic process, we used western blotting and gelatin zymography to examine the effect of GL-V9 on the expression and activity of MMPs. The mechanism revealed that GL-V9 significantly suppressed the expression and activity of MMP-2 and MMP-9. Furthermore, GL-V9 suppressed their upstream protein kinases activation by reducing phosphorylated forms of serine/threonine kinase AKT and c-Jun N-terminal kinase. These findings suggested that GL-V9 could inhibit the invasion of tumor cells by downregulating the expression and activity of MMP-2 and MMP-9, potentially associating with the suppression of phosphorylation of AKT and JNK. [Copyright &y& Elsevier]