Structural Influence of Isothiocyanates on the Antioxidant Response Element (ARE)-Mediated Heme Oxygenase-1 (HO-1) Expression

Prawan, Auemduan; Keum, Young‐Soo; Khor, Tin Oo; Yu, Siwang; Nair, Sreejayan; Li, Wenge; Hu, Longqin; Kong, Ah Ng Tony

doi:10.1007/s11095-007-9370-9

Cited by 62 publications

(57 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanisms other than the direct modulation of DNA methylation status via inhibition of DNMT and histone deacetylating activities may also be important. Sulforaphane, the active isothiocyanate in cruciferous vegetables, has well documented DNA methylation modifying capabilities, but is also known to activate antioxidant stress response proteins such as hemeoxygenase (HO-1) via antioxidant response element (ARE)-mediated and nuclear factor E2-related factor 2 (Nrf2)-mediated gene transcriptional activation mechanisms [Prawan et al, 2007]. Similarly, lycopene (2-6 lM, 16 hr) has been shown to strongly (2-to 4-fold) induce the expression of reporter constructs containing ARE in MCF-7 and hepatocellular carcinoma HepG2 cells [BenDor et al, 2005]; and lycopene induced (>2-fold) mRNA levels of the endogenous ARE-regulated phase II enzymes, NAD(P)H:quinone oxidoreductase (NQO1) and g-glutamylcysteine synthase (GCS) in these cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of gene methylation by genistein or lycopene in breast cancer cells

King-Batoon

Leszczyńska

Klein

2008

Environ and Mol Mutagen

206

113

View full text Add to dashboard Cite

Dietary agents with chemopreventive potential, including soy-derived genistein and tomato-derived lycopene, have been shown to alter gene expression in ways that can either promote or potentially inhibit the carcinogenic processes. To begin to explore the mechanisms by which these agents may be acting we have examined the DNA methylation modulating capacity of genistein or lycopene for several genes relevant to breast cancer in the breast cancer cell lines MCF-7 and MDA-MB-468, as well as in immortalized but noncancer fibrocystic MCF10A breast cells. We find using methylation specific PCR (MSP) that a low, nontoxic concentration of genistein (3.125 lM, resupplemented every 48 hr for 1 week) or a single dose of lycopene (2 lM) partially demethylates the promoter of the GSTP1 tumor suppressor gene in MDA-MB-468 cells. RT-PCR studies confirm a lack of GSTP1 expression in untreated MDA-MB-468, with restoration of GSTP1 expression after genistein or lycopene treatment. The RARb2 gene however, was not demethylated by genistein or lycopene in either of these breast cancer cell lines. But, lycopene (2 lM, once per week for 2 weeks) did induce demethylation of RARb2 and the HIN-1 genes in the noncancer MCF10A fibrocystic breast cells. These data show for the first time that the tomato carotenoid lycopene has direct DNA demethylating activity. In summary, both genistein and lycopene, at very low, dietarily relevant concentrations can potentially mitigate tumorigenic processes via promoter methylation modulation of gene expression. Environ. Mol. Mutagen. 49:36-45, 2008.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of gene methylation by genistein or lycopene in breast cancer cells

King-Batoon

Leszczyńska

Klein

2008

Environ and Mol Mutagen

206

113

View full text Add to dashboard Cite

show abstract

“…In the same cellular model, Keum et al [19] have confirmed that transcriptional activation of Nrf2/ARE is critical in sulforaphanemediated induction of HO-1. Further evidence of the ability of isothiocyanate to activate ARE-mediated HO-1 gene transcription through Nrf2/ARE signaling pathway has been provided by a study from Prawan et al [20] on HepG2-C8 cells.…”

Section: Isothiocyanatesmentioning

confidence: 98%

Natural heme oxygenase-1 inducers in hepatobiliary function

Volti¹,

Sacerdoti²,

Giacomo³

et al. 2008

WJG

View full text Add to dashboard Cite

“…Thus, similar to many chemically unrelated inducers, administration of isothiocyanate to rodents evoked the 'electrophile counter-attack' response. Molecular studies have shown that isothiocyanates can induce phase 2 enzymes by stimulating transcription of phase II genes via a common antioxidant/ electrophile enhancer element (ARE/EpRE) present in the upstream regions of several phase 2 enzyme genes [39] .…”

Section: Mechanism Of Anticarcinogenic Activitymentioning

confidence: 99%

Are isothiocyanates potential anti-cancer drugs?

2009

View full text Add to dashboard Cite

Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

show abstract

Structural Influence of Isothiocyanates on the Antioxidant Response Element (ARE)-Mediated Heme Oxygenase-1 (HO-1) Expression

Cited by 62 publications

References 22 publications

Modulation of gene methylation by genistein or lycopene in breast cancer cells

Modulation of gene methylation by genistein or lycopene in breast cancer cells

Natural heme oxygenase-1 inducers in hepatobiliary function

Are isothiocyanates potential anti-cancer drugs?

Contact Info

Product

Resources

About