title: Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo.
abstract: The thorns of Gleditsia sinensis have traditionally been used in the treatment of several diseases, which includes their use as anti-tumor agents, but there has been no scientific evidence of this anti-tumor effect. However, the present study has identified a novel mechanism for the anti-tumor effect of Gleditsia sinensis thorns in the treatment of colon cancer. Treatment with the ethanol extract of Gleditsia sinensis thorns (EEGS) resulted in significant growth inhibition together with G2/M-phase cell cycle arrest at a dose of 600 microg/ml (IC50) in HCT116 cells. In addition, treatment with EEGS induced p27 expression and down-regulated expression of cyclins and cyclin-dependent kinases. Moreover, EEGS treatment induced phosphorylation of extracellular signal-regulated kinases (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Among the pathways examined, only PD98059 (ERK-specific inhibitor) abolished EEGS-dependent p27 expression. Similarly, suppression of ERK function reversed EEGS-mediated cell proliferation inhibition and decreased cell cycle proteins. In addition, tumor necrosis factor-alpha (TNF-alpha)-induced matrix metalloproteinase-9 (MMP-9) expression was inhibited by EEGS treatment via decreased transcriptional activity of both activator protein-1 (AP-1) and nuclear factor-kappaB. Finally, EEGS treatment significantly reduced tumor sizes in HCT116 cell-xenografted tumor tissues, which was associated with the changed levels of ERK phosphorylation, p27 and MMP-9 expression. Overall, these results have identified a novel molecular mechanism for EEGS in the treatment of colon cancer and might provide a theoretical basis for the potential therapeutic use of EEGS in the treatment of malignancies.
authors.affiliation: Department of Food and Biotechnology, Chungju National University, Chungbuk, Korea.
authors.forename: Se-Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Cho
authors.forename: Heejong
authors.initials: H
authors.lastname: Kim
authors.forename: Keerang
authors.initials: K
authors.lastname: Park
authors.forename: Sung-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Sang-Do
authors.initials: SD
authors.lastname: Ha
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000431:Ethanol / Q000494:pharmacology*; D031501:Gleditsia / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9