Open Access Highly Accessed Research article

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

Ha-Rim Kim110, Jeong-Mi Kim1, Mi-Seong Kim1, Jin-Ki Hwang1, Yeon-Ju Park1, Sei-Hoon Yang2, Hye-Jung Kim3, Do-Gon Ryu4, Dong-Sung Lee5, Hyuncheol Oh567, Youn-Chul Kim567, Yun-Jin Rhee9, Byung-Soon Moon9, Jong-Min Yun9, Kang-Beom Kwon1104* and Young-Rae Lee1108*

Author Affiliations

1 Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, South Korea

2 Department of Internal Medicine, Wonkwang University School of Medicine, Iksan 570-749, South Korea

3 Department of Family Medicine, The Catholic University of Korea, Incheon St. Mary's Hospital, Incheon 403-720, South Korea

4 Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan 570-749, South Korea

5 Hanbang Body-Fluid Research Center, Wonkwang University, #460 Iksan-daero, Iksan, Jeonbuk 570-749, South Korea

6 Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, #460 Iksan-daero, Iksan, Jeonbuk 570-749, South Korea

7 Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, #460 Iksan-daero, Iksan, Jeonbuk 570-749, South Korea

8 Department of Oral Biochemistry, and Institute of Biomaterials, Implant, School of Dentistry, Wonkwang University, Iksan 570-749, South Korea

9 Department of Internal Medicine, College of Korean Medicine, Wonkwang University, #460 Iksan-daero, Iksan City, Jeonbuk 570-749, South Korea

10 BK21plus program & Department of Smart Life-Care Convergence, Wonkwang University, Graduate School, #460 Iksan-daero, Iksan City, Jeonbuk 570-749, South Korea

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

Published: 25 May 2014

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.

Keywords:
Saussurea lappa; MMP-9; Invasion; NF-κB; MCF-7