Impact of Epigenetic Dietary Components on Cancer through Histone Modifications

Gao, Yifeng; Tollefsbol, Trygve O.

doi:10.2174/0929867322666150420102641

Cited by 44 publications

(30 citation statements)

References 188 publications

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“…Epigenetic effects of many isothiocyanates from cruciferous plants ( Brassicaceae ) have been linked to the inhibition of HDAC activity and histone hyperacetylation [300, 434]. In addition, isothiocyanates could alter histone methylation modifications [434, 435].…”

Section: Chromatin Protein Modifications and Natural Compoundsmentioning

confidence: 99%

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

Ratovitski¹

2017

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Accumulating evidence shows that hallmarks of cancer include: “genetic and epigenetic alterations leading to inactivation of cancer suppressors, overexpression of oncogenes, deregulation of intracellular signaling cascades, alterations of cancer cell metabolism, failure to undergo cancer cell death, induction of epithelial to mesenchymal transition, invasiveness, metastasis, deregulation of immune response and changes in cancer microenvironment, which underpin cancer development”. Natural compounds as bioactive ingredients isolated from natural sources (plants, fungi, marine life forms) have revolutionized the field of anticancer therapeutics and rapid developments in preclinical studies are encouraging. Natural compounds could affect the epigenetic molecular mechanisms that modulate gene expression, as well as DNA damage and repair mechanisms. The current review will describe the latest achievements in using naturally produced compounds targeting epigenetic regulators and modulators of gene transcription in vitro and in vivo to generate novel anticancer therapeutics.

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Section: Chromatin Protein Modifications and Natural Compoundsmentioning

confidence: 99%

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

Ratovitski¹

2017

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“…Two H2A-H2B dimers and one H3-H4 tetramer associate to form the histone octamer, which binds to 147 bp of DNA, wrapping 1.65 turns around the histone octamer to form a nucleosome with about 50 bp of DNA between each nucleosome. Histone H1 is called the “linker histone” because rather than forming part of the nucleosome core, it binds the DNA entry/exit points of the nucleosome [9–11]. …”

Section: Introductionmentioning

confidence: 99%

The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer

Abbaoui

Telu

Lucas

et al. 2017

Journal of Proteomics

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Cruciferous vegetable intake is associated with reduced risk of bladder cancer, yet mechanisms remain unclear. Cruciferous vegetable isothiocyanates (ITCs), namely sulforaphane (SFN) and erucin (ECN), significantly inhibit histone deacetylase (HDAC) activity in human bladder cancer cells representing superficial to invasive biology (59–83% inhibition with 20μM, 48h treatment), and in bladder cancer xenografts (59±3% ECN inhibition). Individual HDACs inhibited by SFN and ECN include HDACs 1, 2, 4 and 6. Interestingly, global acetylation status of histones H3 or H4 remain unaltered. The interplay between HDAC inhibition and modest modulation of AcH3 and AcH4 status is partially explained by decreased histone acetyl transferase activity (48.8±5.3%). In contrast, a significant decrease in phosphorylation status of all isoforms of histone H1 was observed, concomitant with increased phosphatase PP1β and PP2A activity. Together, these findings suggest that ITCs modulate histone status via HDAC inhibition and phosphatase enhancement. This allows for reduced levels of histone H1 phosphorylation, a marker correlated with human bladder cancer progression. Therefore, ITC-mediated inhibition of histone H1 phosphorylation presents a novel direction of research in elucidating epidemiological relationships and supports future food-based prevention strategies.

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“…Studies have shown that epigenetic changes can regulate the expression of several tumor-specific genes [10, 11]. We have demonstrated that DNA hypermethylation of CpG islands involving the promoter of tumor suppressor genes can lead to functional loss of these genes in several types of malignancies, including prostate cancer [12–14].…”

Section: Introductionmentioning

confidence: 99%

Functional role and tobacco smoking effects on methylation ofCYP1A1gene in prostate cancer

et al. 2016

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Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2′-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment.

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Impact of Epigenetic Dietary Components on Cancer through Histone Modifications

Cited by 44 publications

References 188 publications

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer

Functional role and tobacco smoking effects on methylation ofCYP1A1gene in prostate cancer

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