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Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway

  • Authors:
    • Qiuyu Wang
    • Peng Wang
    • Zhigang Xiao
  • View Affiliations / Copyright

    Affiliations: College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1887-1898
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    Published online on: January 25, 2018
       https://doi.org/10.3892/ijmm.2018.3423
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Abstract

Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids, and may prevent tumorigenesis of gastrointestinal cancer. Epidemiology and other evidence have suggested that resistant starch may prevent colon cancer development. The aim of the current study was to explore the ameliorative effects and potential mechanisms of resistant starch in the tumorigenesis of colon tumors induced by dimethylhydrazine in C57BL/6 mice. Western blot analysis, ELISA, microscopy, immunofluorescence and immunohistochemistry were used to analyze the efficacy of resistant starch on the metabolic balance in the colon and tumorigenesis of colon tumors. The results demonstrated that a diet containing resistant starch decreased the animal body weight and reduced free ammonia, pH and short chain fatty acids in feces compared with mice that received a standard diet. Resistant starch reduced the incidence of colon tumors and suppressed the expression of carcinogenesis‑associated proteins, including heat shock protein 25, protein kinase C‑d and gastrointestinal glutathione peroxidase in colon epithelial cells compared with standard starch and control groups. Colon tumor cells proliferation and dedifferentiation were significantly decreased by a resistant starch diet. The results also demonstrated that resistant starch increased the apoptosis of colon tumor cells through regulation of apoptosis‑associated gene expression levels in colon tumor cells. Oxidative stress and endoplasmic reticulum stress were upregulated, and elevation eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor‑4 and secretase‑β expression levels were increased in the resistant starch diet group. Additionally, the activity of eIF2α and PERK were increased in colon tumor cells from mice that had received resistant starch. Increasing DNA damage‑inducible transcript 3 protein (CHOP), binding immunoglobulin protein (BIP) and caspase‑12 expression levels upregulated by resistant starch diet may contribute to the resistant starch‑induced apoptosis of colon tumor cells induced by 1,2‑dimethylhydrazine. In vitro assays demonstrated that knockdown of eIF2α inhibited apoptosis of colon tumor cells isolated from mice fed with resistant starch, which also downregulated CHOP, BIP and caspase‑3 expression levels compared with controls. Furthermore, long‑term survival of experimental mice was prolonged by the resistant starch diet compared with the standard diet group. In conclusion, the results indicate that resistant starch in the diet may prevent carcinogenesis of colon epithelial cells, mediated by enhancing apoptosis through an endoplasmic reticulum stress‑mediated mitochondrial apoptosis pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Q, Wang P and Xiao Z: Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway. Int J Mol Med 41: 1887-1898, 2018.
APA
Wang, Q., Wang, P., & Xiao, Z. (2018). Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway. International Journal of Molecular Medicine, 41, 1887-1898. https://doi.org/10.3892/ijmm.2018.3423
MLA
Wang, Q., Wang, P., Xiao, Z."Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway". International Journal of Molecular Medicine 41.4 (2018): 1887-1898.
Chicago
Wang, Q., Wang, P., Xiao, Z."Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway". International Journal of Molecular Medicine 41, no. 4 (2018): 1887-1898. https://doi.org/10.3892/ijmm.2018.3423
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Q, Wang P and Xiao Z: Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway. Int J Mol Med 41: 1887-1898, 2018.
APA
Wang, Q., Wang, P., & Xiao, Z. (2018). Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway. International Journal of Molecular Medicine, 41, 1887-1898. https://doi.org/10.3892/ijmm.2018.3423
MLA
Wang, Q., Wang, P., Xiao, Z."Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway". International Journal of Molecular Medicine 41.4 (2018): 1887-1898.
Chicago
Wang, Q., Wang, P., Xiao, Z."Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway". International Journal of Molecular Medicine 41, no. 4 (2018): 1887-1898. https://doi.org/10.3892/ijmm.2018.3423
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