Abstract
BackgroundSaussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion.MethodsCell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells.ResultsCells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 μM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 μM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells.ConclusionsThese results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.
Highlights
Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities
Our findings demonstrate that ethanol extract of SL (ESL) suppresses TPA-induced Matrix metalloproteinase-9 (MMP-9) expression by blocking the NF-κB signaling pathways, and that the suppression of matrix metalloproteinases (MMPs)-9 expression correlates with inhibited cell invasion
MCF-7 cell viability was not affected by ESL at the concentrations tested (Figure 1A), and for all subsequent experiments, ESL was used at concentrations of 2 or 4 μM
Summary
Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. Most breast cancer deaths are caused by distant metastasis from the primary tumor site. Invasion and metastasis are the fundamental properties and major causes of morbidity and mortality in breast cancer patients. Molecular mechanisms of cancer cell invasion and metastasis involve a complex series of events. One such early event involves proteolytic degradation of the components of the extracellular matrix (ECM) [2], which provides biochemical and mechanical barriers to cell movement in cancer cells [3]. ECM degradation requires extracellular proteinases, of which the matrix metalloproteinases (MMPs) have been shown to play a critical role in breast cancer
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