Suppressive effects of an ethanol extract of Gleditsia sinensis thorns on human SNU-5 gastric cancer cells

Lee,Se-Jung; Ryu,Dong  Hee; Jang,Lee  Chan; Cho,Seok-Cheol; Kim,Wun-Jae; Moon,Sung-Kwon

doi:10.3892/or.2013.2271

Suppressive effects of an ethanol extract of Gleditsia sinensis thorns on human SNU-5 gastric cancer cells

Authors:
- Se-Jung Lee
- Dong Hee Ryu
- Lee Chan Jang
- Seok-Cheol Cho
- Wun-Jae Kim
- Sung-Kwon Moon
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Affiliations: Department of Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, Republic of Korea, Department of Surgery, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361-763, Republic of Korea, Department of Food and Nutrition, Seowon University, Cheongju 361-742, Republic of Korea, Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361-763, Republic of Korea
Published online on: February 4, 2013 https://doi.org/10.3892/or.2013.2271
Pages: 1609-1616

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Abstract

The thorns of Gleditsia sinensis are a traditional Oriental medicine used for the treatment of swelling, suppuration, carbuncle and skin diseases. In the present study, we identified a novel molecular mechanism by which an ethanol extract of Gleditsia sinensis thorns (EEGS) inhibits the growth of the SNU-5 human gastric cancer cell line. EEGS treatment inhibited cell growth and was associated with G1 phase cell cycle arrest at a concentration of 400 µg/ml (IC50) in SNU-5 cells. Treatment with EEGS also stimulated p21WAF1 expression, which significantly decreased the expression of cyclins and cyclin-dependent kinases (CDKs). Further study suggested that p38 MAP kinase pathways may be involved in the inhibition of cell proliferation through p21WAF1‑dependent G1 phase cell cycle arrest in EEGS-treated cells. In addition, NF-κB and AP-1 transcription factor binding sites were identified as the cis-elements for tumor necrosis factor-α (TNF-α)-induced matrix metalloproteinase-9 (MMP-9) expression in SNU-5 cells, as determined by gel-shift assay. Treatment of cells with EEGS suppressed MMP-9 expression induced by TNF-α via a decrease in the binding activity of both NF-κB and AP-1 motifs. These data demonstrate that EEGS-mediated inhibition of cell growth appears to involve the activation of p38 MAP kinase, subsequently leading to the induction of p21WAF1 and the downregulation of cyclin D1/CDK4 and cyclin E/CDK2 complexes. Moreover, EEGS strongly inhibited TNF-α-induced MMP-9 expression by impeding the DNA binding activity of NF-κB and AP-1. Overall, these results provide a potential mechanism for EEGS in the treatment of gastric cancer.

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