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

• Published in: BMC complementary and alternative medicine Vol. 14
• Main Authors: Kim, Ha-Rim, Kim, Jeong-Mi, Kim, Mi-Seong, Hwang, Jin-Ki, Park, Yeon-Ju, Yang, Sei-Hoon, Kim, Hye-Jung, Ryu, Do-Gon, Lee, Dong-Sung, Oh, Hyuncheol, Kim, Youn-Chul, Rhee, Yun-Jin, Moon, Byung-Soon, Yun, Jong-Min, Kwon, Kang-Beom, Lee, Young-Rae
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.01.2014
• Subjects: Binding sites; Breast cancer; Cytokines; Heparan sulfate; Internal medicine; Kinases; Medicine; Metastasis; Pharmaceutical sciences; Pharmacy; Proteins; Studies; Transcription factors
• ISSN: 1472-6882
• DOI: 10.1186/1472-6882-14-170

Doc number: 170 Abstract 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- κB in MCF-7 cells. Results: Cells 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. 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.