Mechanism of oxidative DNA damage induced by carcinogenic allyl isothiocyanate

Murata, Mariko; Yamashita, Naruto; Inoue, Sumiko; Kawanishi, Shosuke

doi:10.1016/s0891-5849(00)00168-4

Cited by 77 publications

(42 citation statements)

References 26 publications

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“…A recent study suggested that the increased expression of cytochrome P450 protein mediates sulforaphane-induced oxidative stress in the lungs of rats (44). Spontaneous hydrolysis of the -N=C=S moiety in isothiocyanates (45) and mitochondrial damage by isothiocyanates (46) may also Figure 6. Effect of sulforaphane/TRAIL cotreatment on hepatoma cells overexpressing Bcl-xL or Bcl-2 and rat primary hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Sensitizes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL)–Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species–Mediated Up-regulation of DR5

Kim

Kim²,

Eom³

et al. 2006

Cancer Research

169

123

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Sulforaphane is a chemopreventive agent present in various cruciferous vegetables, including broccoli. Here, we show that treatment with tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL) in combination with subtoxic doses of sulforaphane significantly induces rapid apoptosis in TRAIL-resistant hepatoma cells. Neither TNF-A-nor Fasmediated apoptosis was sensitized in hepatoma cells by cotreatment with sulforaphane, suggesting that sulforaphane can selectively sensitize cells to TRAIL-induced apoptosis but not to apoptosis mediated by other death receptors. We found that sulforaphane treatment significantly up-regulated mRNA and protein levels of DR5, a death receptor of TRAIL. This was accompanied by an increase in the generation of reactive oxygen species (ROS). Pretreatment with N-acetyl-Lcysteine and overexpression of catalase inhibited sulforaphane-induced up-regulation of DR5 and almost completely blocked the cotreatment-induced apoptosis. Furthermore, the sulforaphane-mediated sensitization to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs for DR5. These results collectively indicate that sulforaphane-induced generation of ROS and the subsequent up-regulation of DR5 are critical for triggering and amplifying TRAIL-induced apoptotic signaling. We also found that sulforaphane can sensitize both Bcl-xL-and Bcl-2-overexpressing hepatoma cells to TRAIL-induced apoptosis, indicating that treatment with a combination of TRAIL and sulforaphane may be a safe strategy for treating resistant hepatomas. (Cancer Res 2006; 66(3): 1740-50)

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Section: Discussionmentioning

confidence: 99%

Sulforaphane Sensitizes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL)–Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species–Mediated Up-regulation of DR5

Kim

Kim²,

Eom³

et al. 2006

Cancer Research

169

123

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“…Second, it has been observed in other studies that prolonged exposure to high levels of electrophilic ITCs in the urine has a carcinogenic effect on bladder epithelium. [24][25][26][27] As GSTM1 or GSTT1 null genotypes have slow ITC metabolism, which leads to extended exposure of ITC metabolites to bladder epithelium, the GSTM1 or GSTT1 null genotypes may not provide an extra protective effect. Furthermore, we observed no significant associations between GSTM1/ GSTT1 polymorphisms and bladder cancer risk in this study, suggesting the effects of genetic modification might be minimal in this study.…”

Section: Discussionmentioning

confidence: 99%

Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk

Zhao¹,

Lin²,

Grossman³

et al. 2007

Intl Journal of Cancer

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TXIsothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. ITCs down-regulate cytochrome P-450 biotransformation enzyme levels, activate Phase II detoxifying enzymes and induce apoptosis. On the other hand, ITCs also serve as a substrate for GSTs. Experimental evidences suggest that ITCs have anticarcinogenic effect on bladder cancer. Therefore, we evaluated dietary intake of ITCs, GSTM1, GSTT1 and NAT2 polymorphisms, and bladder cancer risk in a case-control study. There were 697 newly diagnosed bladder cancer cases identified from The University of Texas M. D. Anderson Cancer Center and 708 healthy controls matched to cases by age (65), gender and ethnicity. Participants underwent an in-person interview, in which epidemiologic and food frequency questionnaires were administered to collect demographic and dietary intake data. Median ITC intake per day was statistically significantly lower in cases than in controls (0.23 vs. 0.33, p < 0.001). High ITC intake was associated with 29% decreased risk of bladder cancer [Odds ratio (OR) 5 0.71, 95% confidence interval (CI) 5 0.57, 0.89]. The protective effect was more evident in older individuals (64-years-old), men, ever smokers and heavy smokers in stratified analysis. Compared with NAT2 rapid acetylator, NAT2 slow acetylator had an increased risk of bladder cancer in Caucasians (OR 5 1.31, 95% CI 5 1.02, 1.69). There was no main effect associated with the GSTM1 or GSTT1 genotypes. The protective effect of ITCs against bladder cancer was not modified by GSTM1, GSTT1 or NAT2 genotypes. This is the first epidemiological report that ITCs from cruciferous vegetable consumption protect against bladder cancer. ' 2007 Wiley-Liss, Inc.

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“…The -N=C=S group of ITC appears to be able to undergo spontaneous hydrolysis leading to the production of superoxide and H 2 O 2 (Murata et al 2000) and the presence of these pro-oxidants in colonocytes could lead to oxidative DNA damage. The hydrolysis of certain GLS present in raw broccoli may result in the generation of nitriles Matusheski et al 2004).…”

Section: Epidemiological Studiesmentioning

confidence: 99%

Cruciferous vegetables and colo-rectal cancer

Lynn

Collins

Fuller³

et al. 2006

Proc. Nutr. Soc.

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Cruciferous vegetables have been studied extensively for their chemoprotective effects. Although they contain many bioactive compounds, the anti-carcinogenic actions of cruciferous vegetables are commonly attributed to their content of glucosinolates. Glucosinolates are relatively biologically inert but can be hydrolysed to a range of bioactive compounds such as isothiocyanates (ITC) and indoles by the plant-based enzyme myrosinase, or less efficiently by the colonic microflora. A number of mechanisms whereby ITC and indoles may protect against colo-rectal cancer have been identified. In experimental animals cruciferous vegetables have been shown to inhibit chemically-induced colon cancer. However, the results of recent epidemiological cohort studies have been inconsistent and this disparity may reflect a lack of sensitivity of such studies. Possible explanations for the failure of epidemiological studies to detect an effect include: assessment of cruciferous vegetable intake by methods that are subject to large measurement errors; the interaction between diet and genotype has not been considered: the effect that post-harvest treatments may have on biological effects of cruciferous vegetables has not been taken into account.

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Mechanism of oxidative DNA damage induced by carcinogenic allyl isothiocyanate

Cited by 77 publications

References 26 publications

Sulforaphane Sensitizes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL)–Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species–Mediated Up-regulation of DR5

Sulforaphane Sensitizes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL)–Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species–Mediated Up-regulation of DR5

Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk

Cruciferous vegetables and colo-rectal cancer

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