Suppression of PMA-induced tumor cell invasion and migration by ginsenoside Rg1 via the inhibition of NF-κB-dependent MMP-9 expression

Abstract

Ginseng has become one of the most commonly used alternative herbal medicines, and its active component, ginsenoside Rg1 has known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have yet to be investigated. In this study, we demonstrated the ability of ginsenoside Rg1 to suppress phorbol myristate acetate (PMA)-induced invasion and migration in MCF-7 breast cancer cells. MCF-7 cells were treated with ginsenoside Rg1 and incubated with or without PMA. The protein and mRNA expression of MMP-9 and MMP-2 was analyzed using Transwell and wound-healing assays and western blotting. The results showed that suppression was associated with the reduced secretion of MMP-9, a key metastatic enzyme. MMP-9 levels were regulated transcriptionally and correlated with the suppression of NF-κB phosphorylation and DNA binding activity. Conversely, ginsenoside Rg1 did not affect MMP-2 mRNA and TIMP-1 mRNA levels, or the activation of AP-1, suggesting a specificity of pathway inhibition. Inhibition of NF-κB activation by p65 small-interfering RNA (siRNA) was shown to suppress PMA-induced cell invasion and migration. The siRNA studies also showed that PMA-induced MMP-9 expression is NF-κB-dependent. The results suggested that the anticancer properties of ginsenoside Rg1 may derive from its ability to inhibit invasion and migration, and that these processes are regulated in breast cancer cells through the NF-κB-mediated regulation of MMP-9 expression.

Inhibition of human colorectal cancer metastasis by notoginsenoside R1, an important compound from Panax notoginseng

“…Our previous study showed that a P. notoginseng ethanol extract inhibited HCT-116 cell migration by significantly decreasing MMP-9 but had no effect on MMP-2 expression (9). Ginsenoside Rg1 also suppressed PMA-induced MMP-9 expression but did not affect MMP-2 expression (38). In the present study, NGR1 was found to regulate MMP-9 expression in the HCT-116 cells.…”

“…Ginsenoside Rg1 also suppressed transforming growth factor β1 (TGF β1)-induced invasion and migration in HepG2 liver cancer cells (36). In addition, by inhibiting MMP-13 expression, ginsenoside Rg3 significantly suppressed the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner (37), and by inhibiting wound healing and MMP-9 expression via suppression of NF-κB phosphorylation and DNA binding activity, ginsenoside Rg1 suppressed phorbol myristate acetate-induced invasion and migration in MCF-7 breast cancer cells (38). The above studies indicate that saponins can reduce the activities of MMPs to inhibit cancer metastasis.…”

Ginsenoside Rb1 attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways

“…Therefore, AAA is defined as a chronic inflammatory condition with a proteolytic imbalance. Ginsenosides have exhibited potential biological functions in AAA suppression, e.g., inhibition of MMP expression and attenuation of the inflammatory response [36][37][38]. However, no direct effect of ginsenosides on AAA development has been reported.…”

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

“…33,34 Exosomes from MCF7 cells or MCF7 cells treated with PMA to increase their malignant potential failed to display thrombotic activity with fibrinogen or human platelet-poor plasma (supplemental Figure 1B). However, thrombotic activity was detected with MVs from MCF7 cells with fibrinogen or human platelet-poor plasma (supplemental Figure 1A), whereas MVs from PMA-treated MCF7 cells displayed thrombotic activity only in the presence of fibrinogen (supplemental Figure 1A).…”