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

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.

• Authors: Se-Jung Lee, Dong Hee Ryu, Lee Chan Jang, Seok-Cheol Cho, Wun-Jae Kim, Sung-Kwon Moon
• Journal: Oncology reports (Oncol Rep) Vol. 29 Issue 4 Pg. 1609-16 (Apr 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23381601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Plant Extracts
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 9

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gleditsia (chemistry)
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Plant Extracts (chemistry, pharmacology)
• Stomach Neoplasms (drug therapy, pathology)
• Tumor Necrosis Factor-alpha (genetics, metabolism)