The Epigenetic Impact of Cruciferous Vegetables on Cancer Prevention

Royston, Kendra J.; Tollefsbol, Trygve O.

doi:10.1007/s40495-014-0003-9

Cited by 87 publications

(62 citation statements)

References 44 publications

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“…Here our observed outcome is inhibition of bladder cancer cell growth by broccoli ITCs, and we see this outcome associated with epigenetic modulations, including acetylation changes of histone H3 and hypo-phosphorylation of histone H1. Future studies will focus on the persistence of the effect of the epigenetic modification and cell viability [32, 48, 49]. …”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Phenethyl isothiocyanate (PEITC), an abundant component of cruciferous vegetables, such as broccoli and watercress, exerts chemoprevention activity by modulating epigenetic modifications[33, 34]. PEITC is a novel epigenetic regulator of both histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), factors that govern the expression and suppression of several genes, including GSTP1 and p21 [35–37].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells

Boyanapalli

Fuentes

et al. 2016

Pharmacological Research

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Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive. The present study aimed to examine the role of PEITC in the epigenetic reactivation of RASSF1A and the induction of apoptosis in LNCaP cells. LNCaP cells were treated for 5 days with 0.01% DMSO, 2.5 or 5 μM PETIC or 2.5 μM azadeoxycytidine (5-Aza) with 0.5 μM trichostatin A (TSA). We evaluated the effects of these treatments on CpG demethylation using methylation-specific polymerase chain reaction (MSP) and bisulfite genomic sequencing (BGS). CpG demethylation was significantly enhanced in cells treated with 5 μM PEITC and 5-Aza+TSA; therefore, the latter treatment was used as a positive control in subsequent experiments. The decrease in RASSF1A promoter methylation correlated with an increase in expression of the RASSF1A gene in a dose-dependent manner. To confirm that promoter demethylation was mediated by DNA methyltransferases (DNMTs), we analyzed the expression levels of DNMTs and histone deacetylases (HDACs) at the gene and protein levels. PEITC reduced DNMT1, 3A and 3B protein levels in a dose-dependent manner, and 5 μM PEITC significantly reduced DNMT3A and 3B protein levels. HDAC1, 2, 4 and 6 protein expression was also inhibited by 5 μM PEITC. The combination of 5-Aza and TSA, a DNMT inhibitor and a HDAC inhibitor, respectively, was used as a positive control as this treatment significantly inhibited both HDACs and DNMTs. The function of RASSF1A reactivation in promoting apoptosis and inducing G2/M cell cycle arrest was analyzed using flow-cytometry analysis with Annexin V and propidium iodide (PI). Growth inhibition effect on LNCaP cells were investigated by colony formation assay. In addition, we analyzed p21, caspase-3 and 7, Bax, and Cyclin B1 protein levels. Flow-cytometry analysis of cells stained with PI alone demonstrated that 5 μM PEITC promotes early apoptosis and G2/M cell cycle arrest. Flow cytometry analysis of cells stained with Annexin V and PI also demonstrated an increased proportion of cells in early apoptosis in cells treated with 5 μM PEITC or 5-Aza with TSA. PEITC and efficiently inhibit colony numbers and total area. In addition, 5 μM PEITC significantly enhanced p21, caspase-3, 7 and Bax levels and reduced Cyclin B1 expression compared with the control group. Collectively, the results of our study suggest that PEITC induces apoptosis in LNCaP cells potentially by reactivating RASSF1A via epigenetic mechanisms.

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“…Naturally occurring phytochemicals have been found to have a wide range of cellular effects (Figure 1). For instance, phytochemicals may prevent carcinogens from reaching targeted sites and support detoxification of highly reactive molecules [21]. Select phytochemicals also enhance innate immune surveillance and improve the elimination of transformed cells [22].…”

Section: An Overview Of Carcinogenesismentioning

confidence: 99%

Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

2016

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Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

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The Epigenetic Impact of Cruciferous Vegetables on Cancer Prevention

Cited by 87 publications

References 44 publications

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

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

Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells

Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

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