Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo

  • Authors:
    • Se-Jung Lee
    • Young-Hwa Cho
    • Heejong Kim
    • Keerang Park
    • Sung-Kyu Park
    • Sang-Do Ha
    • Wun-Jae Kim
    • Sung-Kwon Moon
  • View Affiliations

  • Published online on: December 1, 2009     https://doi.org/10.3892/or_00000594
  • Pages: 1505-1512
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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 µg/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-α (TNF-α)-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-κB. 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.

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December 2009
Volume 22 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee S, Cho Y, Kim H, Park K, Park S, Ha S, Kim W and Moon S: Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo . Oncol Rep 22: 1505-1512, 2009
APA
Lee, S., Cho, Y., Kim, H., Park, K., Park, S., Ha, S. ... Moon, S. (2009). Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo . Oncology Reports, 22, 1505-1512. https://doi.org/10.3892/or_00000594
MLA
Lee, S., Cho, Y., Kim, H., Park, K., Park, S., Ha, S., Kim, W., Moon, S."Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo ". Oncology Reports 22.6 (2009): 1505-1512.
Chicago
Lee, S., Cho, Y., Kim, H., Park, K., Park, S., Ha, S., Kim, W., Moon, S."Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo ". Oncology Reports 22, no. 6 (2009): 1505-1512. https://doi.org/10.3892/or_00000594