Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells

Wang, Yichong; DaCosta, Christopher M.; Wang, Wei; Zhou, Zhigang; Liu, Ming; Bao, Yongping

doi:10.1016/j.nutres.2015.05.011

Cited by 25 publications

(17 citation statements)

References 51 publications

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“…To our knowledge, this study is the first to demonstrate DNA damage reduction and the modulation of Nrf2/ARE pathway by triterpenoids (both CDDO and TRF) in the normal cell line CCD841‐CoN. Although recent work reported that sulforaphane decreased H 2 O 2 ‐mediated oxidative damage and activated the Nrf2/ARE pathway in CCD841 cells, concentrations of 2.5–40 μM were required to elicit this effect. Triterpenoids have been reported to have other relevant bioactivities; oleanolic acid glycosides influence GI transit in mice ; triterpenoids modulate intestinal transport ; purified triterpenoids from Rubus parvifolius , including suavissimoside R1 and coreanoside F1, have antifatigue effects in mice and TRFs from Korean raspberries have potent anti‐inflammatory effects .…”

Section: Discussionmentioning

confidence: 71%

Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

McDougall

Allwood

Pereira-Caro

et al. 2016

Molecular Nutrition Food Res

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Abbreviations: CDDO = 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; FAV = fruit and vegetables; GI = gastrointestinal; TRF = triterpenoid-rich fraction;Key words: Raspberries, metabolic profiling, triterpenoids, colon cancer, ileal fluid ABSTRACT Scope: Ileostomy studies provide a unique insight into digestion of food, allowing identification of physiologically relevant dietary phytochemicals and their metabolites important to gut health. We previously reported the consistent increase of components in ileal fluids of ileostomates after consumption of raspberries with use of non-targeted LC-MS n techniques and data deconvolution software highlighting two major unknown components (m/z 355 and 679). Methods and results:In-depth LC-MS n analyses suggested that the ileal m/z 355 components were p-coumaroyl glucarates. These compounds have not been identified previously and were confirmed in raspberry extracts after partial purification. The major ileal component with m/z 679 was a glycoside with an aglycone of m/z 517 and was present as two peaks in extracts of whole puree, unseeded puree and isolated seeds. These components were purified using Sephadex LH20 and C18 SPE units and identified as major, novel raspberry triterpenoid glycosides. This triterpenoid-enriched fraction (100 nM)protected against H 2 O 2 -induced DNA damage in both colon cancer and normal cell lines and altered expression of cytoprotective genes. Conclusion:The presence of these novel raspberry triterpenoid components in ileal fluids indicates that they would be colon-available in vivo, so confirmation of their anti-cancer bioactivities is of key physiological relevance.www.mnf-journal.comThis article is protected by copyright. All rights reserved.Two major unknown components present in ileal fluids after intake of raspberries were identified as triterpenoid glycosides and p-coumaroyl glucarates using LC-MS n analysis. The triterpenoids were purified from raspberries and were shown to have genoprotective effects at sub-micromolar levels against H 2 O 2 -induced damage in colon cell lines. Therefore these novel triterpenoids combine established colonic bioavailability with potential bioactivity at physiological doses. INTRODUCTIONThere is great interest in the possibility that non-nutritive components could directly contribute to the health benefits attributable to a diet rich in fruit and vegetables (FAV) [1][2][3].One set of phytochemicals of specific interest are the (poly)phenols as are found in high concentrations in certain beverages and FAV, such as berries, and have been attributed a range of important bioactivities [4][5][6][7][8][9]. However, an important issue with ascribing any potential health benefit is the long held view that the bioavailability of many (poly)phenol classes is low. For example, urinary recoveries of anthocyanins, which reflect passage through the circulatory system, are typically <<1% of intake [10], although recent studies with Although previous targeted liquid chromatography mass spectrometry (LC-MS n ) analyses[...

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Section: Discussionmentioning

confidence: 71%

Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

McDougall

Allwood

Pereira-Caro

et al. 2016

Molecular Nutrition Food Res

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show abstract

“…We and others previously showed that Se and dietary phytochemical sulforaphane could synergistically induce TrxR1 through Nrf2 pathway in vitro [19], [20], [21]. This suggests that the interaction of dietary constituents could significantly alter the cellular redox traits.…”

Section: Introductionmentioning

confidence: 76%

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

Dong

Wang

et al. 2016

Redox Biology

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Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system.

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“…The effects of SFN on non-transformed T-lymphocytes were similar to those recorded on Jurkat T-leukaemia cells 30 . SFN showed broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells 31 and regulated the Nrf2/ARE signalling pathway differently in human untransformed epithelial colon cells when compared to colorectal cancer cells 32,33 . Negrette-Guzman et al demonstrated SFN modulates mitochondrial dynamics differentially in normal and cancer cells 34 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Liu

Wang

Tang

et al. 2019

Food and Chemical Toxicology

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Sulforaphane (SFN) has shown anti-cancer effects in cellular and animal studies but its effectiveness has been limited in human studies. Here, the effects of SFN were measured in both human hepatocyte (HHL5) and hepatoma (HepG2) cells. Results showed that SFN inhibited cell viability and induced DNA strand breaks at high doses (≥ 20 µM). It also activated the nuclear factor (erythroidderived 2)-like 2 (Nrf2), and increased intracellular glutathione (GSH) levels at 24 hours. Pretreatment with a low dose SFN (≤5 µM) protected against hydrogen peroxide (H 2 O 2)-induced cell damage. High doses of SFN were more toxic towards HHL5 compared to HepG2 cells; the difference is likely due to the disparity in the responses of Nrf2-driven enzymes and-GSH levels between the two cell lines. In addition, HepG2 cells hijacked the cytoprotective effect of SFN over a wider dose range (1.25-20 µM) compared to HHL5. Manipulation of levels of GSH and Nrf2 in HepG2 cells confirmed that both molecules mediate the protective effects of SFN against H 2 O 2. The non-specific nature of SFN in the regulation of cell death and survival could present undesirable risks, i.e. be more toxic to normal cells, and cause chemo-resistance in tumor cells. These issues should be addressed in the context for cancer prevention and treatment before large scale clinical trials are undertaken.

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Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells

Abstract: 27Dietary isothiocyanates (ITCs) are potent inducers of the NF-E2-related factor-2 (Nrf2)

Cited by 25 publications

References 51 publications

Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

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