Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer

  • Renato Heidor
  • Ernesto Vargas-Mendez
  • Fernando Salvador Moreno
Reference work entry


Bioactive food compounds like vitamin A and the butyrate’s prodrug tributyrin have preventive activities against different types of cancer, and their use in association could represent a promising strategy for cancer treatment and chemoprevention. Both compounds can induce cell differentiation and apoptosis of neoplastic and preneoplastic cells by means of modulation of gene transcription, yet they act through different but interconnected mechanisms. Vitamin A acts through nuclear receptors that are tightly regulated by histone modifications such as acetylation and DNA methylation. Tributyrin modulates transcription of genes by HDACs inhibition and histone hyperacetylation. This chapter describes how epigenetics mediates the antineoplastic and chemopreventive activity of vitamin A, tributyrin, and their derivatives and how their combination can be used to help overcome current limitations in cancer treatment and prevention. We also show how the mechanisms of action of vitamin A and tributyrin have aided in the development of synthetic and bioengineered compounds like synthetic retinoids and structured lipids, respectively.


Cancer chemoprevention Hepatocarcinogenesis Bioactive food compounds Butyrate Tributyrin Vitamin A Retinoids ATRA DNA methylation Histone acetylation HDAC inhibitors 

List of Abbreviations




9-cis retinoic acid


α linolenic acid


Acute promyelocytic leukemia


All-trans retinoic acid


Body weight


Butyric acid


Bioactive food compound


Chromosomal region maintenance 1


Chromatin remodeling complex


DNA methyltransferase


Placental glutathione-S-transferase


Histone 3 acetylated in lysine residue 18


Histone 3 trimethylated in lysine residue 27


Histone 3 acetylated in lysine residue 4


Histone 3 trimethylated in lysine residue 9


Histone 4 acetylated in lysine residue 12


Histone 4 acetylated in lysine residue 16


Histone acetyltransferase


Histone deacetylase


Long interspersed nucleotide element 1


Human homologue of the mouse double minute 2


Nuclear exportation signal


Peroxisomal proliferator activated receptor


Retinoic acid response elements


Retinoic acid receptor alfa


Retinoic acid receptor beta isoform 2


Resistant hepatocyte model




Retinoid X receptors


RXR response elements




Ubiquitin-activating enzyme E1-like


Vitamin D receptor


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Renato Heidor
    • 1
  • Ernesto Vargas-Mendez
    • 1
  • Fernando Salvador Moreno
    • 1
  1. 1.Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil

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