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Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer

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Handbook of Nutrition, Diet, and Epigenetics

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.

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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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Authors and Affiliations

  1. Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil

    Renato Heidor, Ernesto Vargas-Mendez & Fernando Salvador Moreno

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  1. Renato Heidor
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  2. Ernesto Vargas-Mendez
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  3. Fernando Salvador Moreno
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Correspondence to Fernando Salvador Moreno .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Heidor, R., Vargas-Mendez, E., Moreno, F.S. (2019). Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_72

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