Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells
- Equal contributors
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
BMC Complementary and Alternative Medicine 2014, 14:170 doi:10.1186/1472-6882-14-170Published: 25 May 2014
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.
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.
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.
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.