Preventive Effects of Heat-Killed Enterococcus faecalis Strain EC-12 on Mouse Intestinal Tumor Development

Int J Mol Sci. 2017 Apr 13;18(4):826. doi: 10.3390/ijms18040826.

Abstract

Establishing effective methods for preventing colorectal cancer by so-called "functional foods" is important because the global burden of colorectal cancer is increasing. Enterococcus faecalis strain EC-12 (EC-12), which belongs to the family of lactic acid bacteria, has been shown to exert pleiotropic effects, such as anti-allergy and anti-infectious effects, on mammalian cells. In the present study, we aimed to evaluate the preventive effects of heat-killed EC-12 on intestinal carcinogenesis. We fed 5-week-old male and female Apc mutant Min mice diets containing 50 or 100 ppm heat-killed EC-12 for 8 weeks. In the 50 ppm treated group, there was 4.3% decrease in the number of polyps in males vs. 30.9% in females, and significant reduction was only achieved in the proximal small intestine of female mice. A similar reduction was observed in the 100 ppm treated group. Moreover, heat-killed EC-12 tended to reduce the levels of c-Myc and cyclin D1 mRNA expression in intestinal polyps. Next, we confirmed that heat-killed EC-12 suppressed the transcriptional activity of the T-cell factor/lymphoid enhancer factor, a transcriptional factor involved in cyclin D1 mRNA expression in intestinal polyps. Our results suggest that heat-killed EC-12 very weakly suppresses intestinal polyp development in Min mice, in part by attenuating β-catenin signaling, and this implies that heat-killed EC-12 could be used as a "functional food".

Keywords: Min mice; colorectal cancer chemoprevention; functional foods; heat-killed EC-12; intestinal polyps.

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Chemoprevention
  • Colorectal Neoplasms / prevention & control*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Diet
  • Enterococcus faecalis / genetics
  • Enterococcus faecalis / physiology*
  • Face / microbiology
  • Female
  • Functional Food / microbiology
  • HCT116 Cells
  • Hot Temperature
  • Humans
  • Intestinal Polyps / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger
  • Signal Transduction
  • TCF Transcription Factors / genetics
  • TCF Transcription Factors / metabolism
  • Transcriptional Activation
  • beta Catenin / metabolism

Substances

  • DNA, Bacterial
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • TCF Transcription Factors
  • beta Catenin
  • Cyclin D1