Korean Red Ginseng Suppresses Metastasis of Human Hepatoma SK-Hep1 Cells by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase Plasminogen Activator

Abstract

Korean red ginseng and ginsenosides have been claimed to possess wide spectrum of medicinal effects, of which anticancer effect is one. The present study was undertaken to investigate the antimetastatic effect of Korean red ginseng on human hepatoma as well as possible mechanisms. The inhibitory effect of the water extract of Korean red ginseng (WKRG) on the invasion and motility of SK-Hep1 cells was evaluated by the Boyden chamber assay in vitro. Without causing cytotoxicity, WKRG exerted a dose-dependent inhibitory effect on the invasion and motility, but not adhesion, of highly metastatic SK-Hep1 cells. Zymography analyses revealed significant downregulating effects on MMP-2, MMP-9, and uPA activities in SK-Hep1 cells. Western blot analyses also showed that WKRG treatment caused dose-dependent decreases in MMP-2 and MMP-9 protein expressions. Moreover, WKRG increased the levels of TIMP-1, TIMP-2, and PAI-1. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by WKRG, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 and uPA expressions of SK-Hep1 cells.

Ginseng and Its Active Components Ginsenosides Inhibit Adipogenesis in 3T3-L1 Cells by Regulating MMP-2 and MMP-9

“…Our results are supported by several lines of evidence indicating that ginseng inhibits MMP-2 and MMP-9 expression and activity; GE suppresses the metastasis of human hepatoma SK-Hep1 cells by inhibiting MMP-2 and MMP-9 [19], and GSs including Rb1, Rb2, Rd, and Rg3 inhibit MMP-2 and MMP-9 protein expression and activity in several types of cells such as SKOV-3 ovarian cancer cells and HepG2 human hepatoma cells [15–18, 30, 31], suggesting that the inhibition of MMP activity is important in terms of preventing cell metastasis. Although many reports indicated that ginseng prevents cell metastasis by inhibiting MMP activity, there is no evidence demonstrating that MMP inhibition by ginseng regulates adipogenesis.…”

“…Ginseng has also been reported to inhibit tumor growth by modulating MMP-2 and MMP-9 [15, 16], which are regarded as markers of tumor invasion and metastasis, and suppression of their expression may inhibit malignant tumor invasion and metastasis. Ginseng and ginsenosides (GSs), its major active components, exhibit potential as potent cancer chemopreventive agents due in part to their downregulation of MMP expression [15–19]. Based on the well-documented regulation of adipogenesis by MMPs and regulation of MMP expression by ginseng, we hypothesized that ginseng and GSs can inhibit adipogenesis in 3T3-L1 adipocytes.…”

7‐Methoxy‐luteolin‐8‐C‐β‐6‐deoxy‐xylo‐pyranos‐3‐uloside exactly (mLU8C‐PU) isolated from Arthraxon hispidus inhibits migratory and invasive responses mediated via downregulation of MMP‐9 and IL‐8 expression in MCF‐7 breast cancer cells

“…The MMP family can be divided into the following five groups: collagenases (MMP‐1, MMP‐8, MMP‐13, and MMP‐18), stromalysines (MMP‐3, MMP‐10, and MMP‐11), matrilysines (MMP‐7 and MMP‐26), membrane‐bound MMPs (MMP‐14, MMP‐15, MMP‐16, MMP‐17, MMP‐24, and MMP‐25), and gelatinases (MMP‐2 and MMP‐9) . Among these, MMP‐2 and MMP‐9 are the major enzyme involved in breast cancer cell invasion and metastasis . The overexpression of MMP‐9 is essential for tumor invasion.…”

Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9

“…MMPs have significant roles in cancer metastasis. Furthermore, the activity of MMP-2/9 is associated with the adhesion, invasion and angiogenesis of cancer metastasis (34,35). Therefore, the effect of ophiopogonin-D on the expression of MMP-2 and MMP-9 was deteced by western blot analysis.…”