1. Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo
- Author
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Sang-Do Ha, Wun-Jae Kim, Hee Jong Kim, Young-Hwa Cho, Keerang Park, Sung-Kwon Moon, Sung-Kyu Park, and Se-Jung Lee
- Subjects
MAPK/ERK pathway ,Cancer Research ,medicine.medical_specialty ,p38 mitogen-activated protein kinases ,Pharmacology ,p38 Mitogen-Activated Protein Kinases ,Inhibitory Concentration 50 ,Mice ,Cell Line, Tumor ,Internal medicine ,Gleditsia ,medicine ,Animals ,Humans ,Dose-Response Relationship, Drug ,Ethanol ,biology ,Oncogene ,Plant Extracts ,Tumor Necrosis Factor-alpha ,Cell growth ,Kinase ,Cell Cycle ,General Medicine ,Cell cycle ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Gleditsia sinensis ,Endocrinology ,Matrix Metalloproteinase 9 ,Oncology ,Mitogen-activated protein kinase ,biology.protein ,Drug Screening Assays, Antitumor - 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.
- Published
- 2009