Histone Deacetylase Modifications by Probiotics in Colorectal Cancer

J Gastrointest Cancer. 2020 Sep;51(3):754-764. doi: 10.1007/s12029-019-00338-2.

Abstract

It has been demonstrated that epigenetic modifications of histone (acetylation/deacetylation) participate in a critical role in cancer progression by the regulation of gene expression. Several processes could be regulated by deacetylation of histone and non-histone proteins such as apoptosis, proliferation, cell metabolism, differentiation, and DNA repair. Hence, histone deacetylase inhibitors (HDACis) are employed as a hopeful group of anti-cancer drugs that could inhibit tumor cell proliferation or apoptosis. The elimination of the acetylation marks that take place as an essential epigenetic change in cancer cells is associated to HDAC expression and activity. In this regard, it has been reported that class I HDACs have a vital role in the regulation of tumor cell proliferation. OBJECTIVES: In this review, we discuss whether gut origin microorganisms could promote cancer or tumor resistance and explain mechanisms of these processes. CONCLUSIONS: According to the enormous capacity of the metabolism of the intestine microbiota, bacteria are likely to convert nutrients and digestive compounds into metabolites that regulate epigenetic in cancer. The effect of the food is of interest on epigenetic changes in the intestinal mucosa and colonocytes, as misleading nucleotide methylation may be a prognostic marker for colorectal cancer (CRC). Since epigenetic changes are potentially reversible, they can serve as therapeutic targets for preventing CRC. However, various mechanisms have been identified in the field of prevention, treatment, and progression of cancer by probiotics, which include intestinal microbiota modulation, increased intestinal barrier function, degradation of potential carcinogens, protective effect on intestinal epithelial damage, and increased immune function.

Keywords: Colorectal cancer; Epigenetic; Histone deacetylase; Probiotic.

Publication types

  • Review

MeSH terms

  • Acetylation / drug effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / microbiology
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy / methods
  • Dietary Fiber / administration & dosage
  • Disease Progression
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / immunology
  • Gastrointestinal Microbiome / physiology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism*
  • Histones / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Prebiotics / administration & dosage
  • Probiotics / administration & dosage*

Substances

  • Dietary Fiber
  • Histone Deacetylase Inhibitors
  • Histones
  • Prebiotics
  • Histone Deacetylases