Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Abstract

Significance: Sulforaphane, produced by the hydrolytic conversion of glucoraphanin after ingestion of cruciferous vegetables, particularly broccoli and broccoli sprouts, has been extensively studied due to its apparent health-promoting properties in disease and limited toxicity in normal tissue. Recent Studies: Recent identification of a sub-population of tumor cells with stem cell-like self-renewal capacity that may be responsible for relapse, metastasis, and resistance, as a potential target of the dietary compound, may be an important aspect of sulforaphane chemoprevention. Evidence also suggests that sulforaphane may target the epigenetic alterations observed in specific cancers, reversing aberrant changes in gene transcription through mechanisms of histone deacetylase inhibition, global demethylation, and microRNA modulation. Critical Issues: In this review, we discuss the biochemical and biological properties of sulforaphane with a particular emphasis on the anticancer properties of the dietary compound. Sulforaphane possesses the capacity to intervene in multistage carcinogenesis through the modulation and/or regulation of important cellular mechanisms. The inhibition of phase I enzymes that are responsible for the activation of pro-carcinogens, and the induction of phase II enzymes that are critical in mutagen elimination are well-characterized chemopreventive properties. Furthermore, sulforaphane mediates a number of anticancer pathways, including the activation of apoptosis, induction of cell cycle arrest, and inhibition of NFjB. Future Directions: Further characterization of the chemopreventive properties of sulforaphane and its capacity to be selectively toxic to malignant cells are warranted to potentially establish the clinical utility of the dietary compound as an anticancer compound alone, and in combination with clinically relevant therapeutic and management strategies.

Activation of Nrf2 by Sulforaphane Inhibits High Glucose-Induced Progression of Pancreatic Cancer via AMPK Dependent Signaling

“…It has been reported that SFN can combat cancer by multiple mechanisms, including induce Nrf2 activation [36], epigenetic modulation of oncogenic MicroRNA-21 and human telomerase reverse transcriptase (hTERT) [37], inhibition of histone deacetylase (HDAC) [38] and NF-κB [39]. However, its anti-tumor effect on pancreatic cancer, especially under high glucose conditions, has not been investigated.…”

Sinapinic and protocatechuic acids found in rapeseed: isolation, characterisation and potential benefits for human health as functional food ingredients

“…The study found that when isolating polyphenols from rapeseed cake, the liquid-to-solid ratio was a key parameter. The highest and apoptosis (Tortorella et al, 2015). Thus, HDAC inhibitors are emerging as potential therapeutic agents.…”

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

“…Histone tails can be modified by acetylation, methylation, phosphorylation, poly-ADP ribosylation, sumoylation, ubiquitination, citrullination, and proline isomerization (Jenuwein and Allis 2001;Tollefsbol 2009). Histone posttranslational modifications are complex, dynamic, and highly coordinated in chromatin remodeling and gene regulation.…”

“…Histone posttranslational modifications are complex, dynamic, and highly coordinated in chromatin remodeling and gene regulation. Different combinations of histone modification and histone variants, often referred as "histone code," determine the interactions of histones with DNA and regulate the chromatin structure and its accessibility to transcription factors (Margueron et al 2005;Tollefsbol 2009). …”

“…Histone acetylation causes decondensation of chromatin, thus allowing its accessibility to transcriptional factors (Tollefsbol 2009). The reverse process is histone deacetylation, catalyzed by HDACs, which leads to chromatin condensation and the suppression of DNA transcription (Mahlknecht and Hoelzer 2000) (Fig.…”