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

• Published in: Oncology reports Vol. 29; no. 4; pp. 1609 - 1616
• Main Authors: LEE, SE-JUNG, RYU, DONG HEE, JANG, LEE CHAN, CHO, SEOK-CHEOL, KIM, WUN-JAE, MOON, SUNG-KWON
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.04.2013; Spandidos Publications UK Ltd
• Subjects: Antineoplastic Agents - pharmacology; AP-1; Apoptosis; Apoptosis - drug effects; Cancer therapies; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; Ethanol; Extracellular matrix; G1 phase cell cycle arrest; Gastric cancer; Gene Expression Regulation, Neoplastic - drug effects; Gleditsia - chemistry; Gleditsia sinensis thorns; Humans; Kinases; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Metastasis; MMP-9; NF-κB; p21WAF1; p38 MAP kinase; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polyclonal antibodies; Proteins; Regulation; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Studies; Transcription factors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2013.2271

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-αB 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.