J Vet Sci.  2022 Sep;23(5):e74. 10.4142/jvs.22097.

Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation

  • 1College of Veterinary Medicine and Veterinary Medicine Center, Chungbuk National University, Cheongju 28644, Korea
  • 2Korea Food Culture Promotion Association, Cheongju 28553, Korea
  • 3Department of Biotechnology and Biomedicine, Chungbuk Provincial University, Cheongju 28160, Korea
  • 4Department of Neurosurgery, Chungbuk National University Hospital, Cheongju 28644, Korea
  • 5Department of Medical Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
  • 6Institute for Stem Cell & Regenerative Medicine (ISCRM), Chungbuk National University, Cheongju 28644, Korea
  • 7Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea
  • 8Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea


Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meatassociated colon carcinogenesis is not well understood.
We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action.
Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model.
In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model.
We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.


Hemin; colon cancer; epigallocatechin-3-gallate; reactive oxygen species; oxidative stress; nuclear respiratory factor 2
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