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Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer

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

Abstract

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.

Keywords

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

List of Abbreviations

5-aza

5-azacytidine

9cRA

9-cis retinoic acid

ALA

α linolenic acid

APL

Acute promyelocytic leukemia

ATRA

All-trans retinoic acid

b.w.

Body weight

BA

Butyric acid

BFC

Bioactive food compound

Crm-1

Chromosomal region maintenance 1

CRP

Chromatin remodeling complex

DNMT

DNA methyltransferase

GST-P

Placental glutathione-S-transferase

H3K18ac

Histone 3 acetylated in lysine residue 18

H3K27me3

Histone 3 trimethylated in lysine residue 27

H3K4ac

Histone 3 acetylated in lysine residue 4

H3K9me3

Histone 3 trimethylated in lysine residue 9

H4K12ac

Histone 4 acetylated in lysine residue 12

H4K16ac

Histone 4 acetylated in lysine residue 16

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

LINE-1

Long interspersed nucleotide element 1

Mdm2

Human homologue of the mouse double minute 2

NES

Nuclear exportation signal

PPAR

Peroxisomal proliferator activated receptor

RARE

Retinoic acid response elements

RARα

Retinoic acid receptor alfa

RARβ2

Retinoic acid receptor beta isoform 2

RH

Resistant hepatocyte model

ROL

Retinol

RXR

Retinoid X receptors

RXRE

RXR response elements

TB

Tributyrin

UBE1L

Ubiquitin-activating enzyme E1-like

VDR

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
    Email author
  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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