Regulation of NF-E2-Related Factor 2 Signaling for Cancer Chemoprevention: Antioxidant Coupled with Antiinflammatory

Hu, Rong; Saw, Constance Lay Lay; Yu, Rong; Kong, Ah‐Ng Tony

doi:10.1089/ars.2010.3276

Cited by 173 publications

(144 citation statements)

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“…It has been reported that inducible Nrf2 activation reduces carcinogenesis, especially in its early stages (12)(13)(14). It has been shown that inducible Nrf2 activation is important in the anticancer effects of many natural compounds, including phenethyl isothiocyanate, curcumin, and resveratrol (12 859-323-1059; E-mail: xshi5@email.uky.edu.…”

mentioning

confidence: 99%

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Son

Pratheeshkumar

Roy

et al. 2015

Journal of Biological Chemistry

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Background: Arsenic induced cell transformation and carcinogenesis. Results: Arsenic-transformed cells have the property of apoptosis/autophagy resistance. Conclusion:The constitutive activation of Nrf2 in arsenic-transformed cells up-regulates antioxidants, decreases ROS generation, and causes apoptosis resistance and tumorigenesis. Significance: Antioncogenic role of inducible Nrf2 in normal cells and oncogenic role of constitutive activation of Nfr2 in cancer cells may increase our understanding of the mechanism of arsenic carcinogenesis and its prevention.

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confidence: 99%

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Son

Pratheeshkumar

Roy

et al. 2015

Journal of Biological Chemistry

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“…and either D-G1 or D-G2 was found to significantly reduce the methylation of the five CpGs (37.6% and 54.4%, respectively; Fisher's exact test, p<0.001). Moreover, compared with the two treated groups, it was found that D-G1 has significantly lower level of methylation than D-G2 (Fisher's exact test, p00.011) Nrf2 is a redox sensitive transcriptional factor and plays a very important role in the cellular defense against oxidative and inflammatory stresses (8). Our previous studies show that, as prostatic tumor progresses in TRAMP mice, there is a decrease in the expression of Nrf2 and Nrf2 downstream target antioxidative stress genes (5,32).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays a critical role in the antioxidative stress response including the coordinated regulation of many detoxifying/antioxidant enzymes (7,8). Recently, a progressive loss of Nrf2 expression as well as Nrf2 downstream target genes has been demonstrated in clinical prostate cancer patients (6).…”

Section: Introductionmentioning

confidence: 99%

“…In our current study, we examined the epigenetic modifications of the promoter of Nrf2, a critical transcription factor in mediating cellular defense against oxidative stress and inflammation (8,20), in vitro in TRAMP-C1 cells. Following that, we further investigated the inhibitory efficacy of prostate tumorigenesis and epigenetic modifications of DIM in vivo in TRAMP mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors

Khor

et al. 2013

AAPS J

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Abstract. 3,3′-diindolylmethane (DIM) is currently being investigated in many clinical trials including prostate, breast, and cervical cancers and has been shown to possess anticancer effects in several in vivo and in vitro models. Previously, DIM has been reported to possess cancer chemopreventive effects in prostate carcinogenesis in TRAMP mice; however, the in vivo mechanism is unclear. The present study aims to investigate the in vitro and in vivo epigenetics modulation of DIM in TRAMP-C1 cells and in TRAMP mouse model. In vitro study utilizing TRAMP-C1 cells showed that DIM suppressed DNMT expression and reversed CpG methylation status of Nrf2 resulting in enhanced expression of Nrf2 and Nrf2-target gene NQO1. In vivo study, TRAMP mice fed with DIM-supplemented diet showed much lower incidence of tumorigenesis and metastasis than the untreated control group similar to what was reported previously. DIM increased apoptosis, decreased cell proliferation and enhanced Nrf2 and Nrf2-target gene NQO1 expression in prostate tissues. Importantly, immunohistochemical analysis showed that DIM reduced the global CpG 5-methylcytosine methylation. Focusing on one of the early cancer chemopreventive target gene Nrf2, bisulfite genomic sequencing showed that DIM decreased the methylation status of the first five CpGs of the Nrf2 promoter region, corroborating with the results of in vitro TRAMP-C1 cells. In summary, our current study shows that DIM is a potent cancer chemopreventive agent for prostate cancer and epigenetic modifications of the CpG including Nrf2 could be a potential mechanism by which DIM exerts its chemopreventive effects.

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“…A major proportion of the effects of SFN seems to be mediated via antioxidant response elements (ARE) and the transcription factor NF-E2-related factor 2 (Nrf2) (5,14). Nrf2 regulates the transcription of cytoprotective genes, which promote cell protection toward oxidative damage (15) and enhance resistance to carcinogenesis (16). Chemically induced cancer formation is enhanced in Nrf2-deficient mice (17), supporting the protective role of SFN and Nrf2 activation in early carcinogenesis.…”

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confidence: 95%

Sulforaphane Protects from T Cell–Mediated Autoimmune Disease by Inhibition of IL-23 and IL-12 in Dendritic Cells

Geisel

Brück

Glocova

et al. 2014

The Journal of Immunology

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Sulforaphane (SFN), an isothiocyanate, is part of an important group of naturally occurring small molecules with anti-inflammatory properties. The published reports are best conceivable with an inhibition of T cell function, but the mode of action remains unknown. We therefore analyzed the effect of SFN on T cell–mediated autoimmune disease. Feeding mice with SFN protected from severe experimental autoimmune encephalomyelitis. Disease amelioration was associated with reduced IL-17 and IFN-γ expression in draining lymph nodes. In vitro, SFN treatment of T cells did not directly alter T cell cytokine secretion. In contrast, SFN treatment of dendritic cells (DCs) inhibited TLR4-induced IL-12 and IL-23 production, and severely suppressed Th1 and Th17 development of T cells primed by SFN-treated DCs. SFN regulated the activity of the TLR4-induced transcription factor NF-κB, without affecting the degradation of its inhibitor IκB-α. Instead, SFN treatment of DCs resulted in strong expression of the stress response protein heme oxygenase-1 (HO-1), which interacts with and thereby inhibits NF-κB p65. Consistent with these findings, HO-1 bound to p65 and subsequently inhibited the p65 activity at the IL23a and IL12b promoters. Importantly, SFN suppressed Il23a and Il12b expression in vivo and silenced Th17/Th1 responses within the CNS. Thus, our data show that SFN improves Th17/Th1-mediated autoimmune disease by inducing HO-1 and inhibiting NF-κB p65-regulated IL-23 and IL-12 expression.

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Regulation of NF-E2-Related Factor 2 Signaling for Cancer Chemoprevention: Antioxidant Coupled with Antiinflammatory

Abstract: Cancer chemoprevention is a process of using either natural or synthetic compounds to reduce the risk of developing cancer. Observations that NF-

Cited by 173 publications

References 173 publications

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors

Sulforaphane Protects from T Cell–Mediated Autoimmune Disease by Inhibition of IL-23 and IL-12 in Dendritic Cells

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