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Open Access Highly Accessed Research article

Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-kappaB-dependent MMP-9 expression in MCF-7 breast cancer cells

Ha-Rim Kim, Jeong-Mi Kim, Mi-Seong Kim, Jin-Ki Hwang, Yeon-Ju Park, Sei-Hoon Yang, Hye-Jung Kim, Do-Gon Ryu, Dong-Sung Lee, Hyuncheol Oh, Youn-Chul Kim, Yun-Jin Rhee, Byung-Soon Moon, Jong-Min Yun, Kang-Beom Kwon and Young-Rae Lee

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BMC Complementary and Alternative Medicine 2014, 14:170  doi:10.1186/1472-6882-14-170

Published: 25 May 2014

Abstract (provisional)

Background

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. 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.

Methods

Cell 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- kappaB in MCF-7 cells.

Results

Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 muM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 muM) 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-kappaB). 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.

Conclusions

These 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.

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