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

ABSTRACT: 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 20?M, 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 PP1? 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.Collectively, our findings suggest that the cruciferous vegetable isothiocyanates: sulforaphane (SFN) and erucin (ECN), impact histones status in bladder cancer cells by modulating specific HDACs and HATs, and enhancing phosphatase activity, resulting in reduction of histone H1 phosphorylation. These findings are significant due to the fact that our previous work positively correlated histone H1 phosphorylation with bladder cancer carcinogenesis and progression. Therefore, we propose that SFN and ECN may inhibit bladder carcinogenesis via epigenetic modulation of gene expression associated with histone H1 phosphorylation. These efforts may elucidate biomarkers useful in epidemiologic studies related to cruciferous vegetable intake and cancer risk or provide intermediate biomarkers for food-based clinical intervention studies in high-risk cohorts.

SUBMITTER: Abbaoui B

PROVIDER: S-EPMC5324139 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Abbaoui Besma B Telu Kelly H KH Lucas Christopher R CR Thomas-Ahner Jennifer M JM Schwartz Steven J SJ Clinton Steven K SK Freitas Michael A MA Mortazavi Amir A

Journal of proteomics 20170127

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 ...[more]

PMID: 28132875

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Project description:BackgroundBladder cancer is one of the top 10 most common cancers in the United States. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed surgically. However, 50% to 80% of NMIBC cases recur within 5 years, and 15% to 30% progress with poor survival. Current treatments are limited and expensive. A wealth of preclinical and epidemiological evidence suggests that dietary isothiocyanates in cruciferous vegetables (Cruciferae) could be a novel, noninvasive, and cost-effective strategy to control NMIBC recurrence and progression.ObjectiveThe aim of this study is to develop a scalable dietary intervention that increases isothiocyanate exposure through Cruciferae intake in NMIBC survivors.MethodsWe worked with a community advisory board (N=8) to identify relevant factors, evidence-based behavior change techniques, and behavioral theory constructs used to increase Cruciferae intake in NMIBC survivors; use the PEN-3 Model focused on incorporating cultural factors salient to the group's shared experiences to review the intervention components (eg, the saliency of behavioral messages); administer the revised intervention to community partners for their feedback; and refine the intervention.ResultsWe developed a multicomponent intervention for NMIBC survivors consisting of a magazine, tracking book, live telephone call script, and interactive voice messages. Entitled POW-R Health: Power to Redefine Your Health, the intervention incorporated findings from our adaptation process to ensure saliency to NMIBC survivors.ConclusionsThis is the first evidence-based, theoretically grounded dietary intervention developed to reduce bladder cancer recurrence in NMIBC survivors using a systematic process for community adaptation. This study provides a model for others who aim to develop behavioral, community-relevant interventions for cancer prevention and control with the overall goal of wide-scale implementation and dissemination.

Project description:Background: The chemopreventive activities of cruciferous vegetables were recognized in the early 1990s, followed by a growth of evidence in various cancer models, including breast cancer. To our knowledge, no studies have examined whether consumption of cruciferous vegetables has changed accordingly, and what impact, if any, on breast cancer risk may have resulted. Objective: The time trend in cruciferous vegetable intake was investigated between 1982 and 1998, and its associations with breast cancer risk were examined. Methods: In a hospital-based case-control study in 1491 patients with breast cancer and 1482 controls, loess curves were constructed to describe the relation between median consumption of cruciferous vegetables and year of admission. ORs and 95% CIs were calculated with unconditional logistic regression, adjusting for age, year of admission, family income, body mass index, cigarette smoking, age at menarche, parity, age at first birth, family history of breast cancer, hormone replacement therapy, and total meat intake. Results: Consumption patterns differed between cases and controls. A slow but steady increase in cruciferous vegetable intake was observed in the cases, although among controls, cruciferous vegetable consumption increased from 1982 to 1987, reached a plateau during 1988-1992, and then declined from 1993 to 1998. Accordingly, although an overall inverse association with breast cancer risk was observed for cruciferous vegetable intake (highest compared with lowest quartile-OR: 0.68; 95% CI: 0.55, 0.86; P-trend = 0.0006), the inverse association tended to be more pronounced within more recent-year strata, with an OR of 0.52 (95% CI: 0.33, 0.83) for 1993-1998 compared with an OR of 0.89 (95% CI: 0.64, 1.23) for 1982-1987. Conclusions: The consumption of cruciferous vegetables increased during the past 2 decades, showing different trends in cases and controls. The subtle but sustained increase in cruciferous vegetable intake reported by the cases could influence association studies with breast cancer risk.

Dataset Information

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

Publications

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

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