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Article

Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis

  • Authors:
    • Takuya Inoue
    • Naoki Yorifuji
    • Munetaka Iguchi
    • Kaori Fujiwara
    • Kazuki Kakimoto
    • Sadaharu Nouda
    • Toshihiko Okada
    • Ken Kawakami
    • Yosuke Abe
    • Toshihisa Takeuchi
    • Kazuhide Higuchi
  • View Affiliations / Copyright

    Affiliations: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan
  • Pages: 1769-1774
    |
    Published online on: February 10, 2015
       https://doi.org/10.3892/or.2015.3794
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Abstract

Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. GGA protects a variety of cells and tissues against numerous stresses via induction of heat shock protein (HSP) 70, and it has recently been reported to protect mice from experimental ulcerative colitis (UC). However, it is unknown whether GGA exhibits a preventive effect on UC-associated neoplasia. In the present study, we evaluated the preventive effects of GGA on colitis-related carcinogenesis in the mouse colon. Mice were administered 1,2-dimethylhydrazine (DMH) subcutaneously three times within a week, followed by 2 cycles of dextran sulfate sodium (DSS) (each cycle, 3% DSS for 7 days and then distilled water for 14 days) and they were sacrificed 28 days after the completion of the 2 cycles. The mice were divided into the following groups according to the diet received during the experiment: group A, which received a standard diet and served as a disease control; group B, which received a diet mixed with 0.25% GGA; group C, which received a diet mixed with 0.5% GGA; group D, which received a diet mixed with 1.0% GGA; group E, which received a diet mixed with 2.0% GGA; and group F, which received a diet containing no agents, including DSS and served as a normal control. The incidence of neoplasia was assessed. The expression of inducible nitric oxide synthase (iNOS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also determined. In addition, the expression of HSP70 in the colon tissues was determined by immunohistochemistry and western blot analysis. The mean number of tumors was 16.6, 11.0, 9.4, 5.8, 5.4 and 0 in groups A-F, respectively. GGA significantly suppressed the occurrence of neoplasia in a dose-dependent manner. GGA treatment enhanced the expression of HSP70 and suppressed the oxidative damage in the background mucosa (i.e. lesion-free colon). These results suggest that GGA could be useful in the prevention of UC-associated neoplasia.
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Copy and paste a formatted citation
Spandidos Publications style
Inoue T, Yorifuji N, Iguchi M, Fujiwara K, Kakimoto K, Nouda S, Okada T, Kawakami K, Abe Y, Takeuchi T, Takeuchi T, et al: Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis. Oncol Rep 33: 1769-1774, 2015.
APA
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S. ... Higuchi, K. (2015). Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis. Oncology Reports, 33, 1769-1774. https://doi.org/10.3892/or.2015.3794
MLA
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis". Oncology Reports 33.4 (2015): 1769-1774.
Chicago
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis". Oncology Reports 33, no. 4 (2015): 1769-1774. https://doi.org/10.3892/or.2015.3794
Copy and paste a formatted citation
x
Spandidos Publications style
Inoue T, Yorifuji N, Iguchi M, Fujiwara K, Kakimoto K, Nouda S, Okada T, Kawakami K, Abe Y, Takeuchi T, Takeuchi T, et al: Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis. Oncol Rep 33: 1769-1774, 2015.
APA
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S. ... Higuchi, K. (2015). Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis. Oncology Reports, 33, 1769-1774. https://doi.org/10.3892/or.2015.3794
MLA
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis". Oncology Reports 33.4 (2015): 1769-1774.
Chicago
Inoue, T., Yorifuji, N., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis". Oncology Reports 33, no. 4 (2015): 1769-1774. https://doi.org/10.3892/or.2015.3794
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