title: 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: Department of Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, Republic of Korea.
authors: Se-Jung
authors: SJ
authors: Lee
authors: Dong Hee
authors: DH
authors: Ryu
authors: Lee Chan
authors: LC
authors: Jang
authors: Seok-Cheol
authors: SC
authors: Cho
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D031501:Gleditsia / Q000737:chemistry*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9