Inhibition of Mutagenicity of Food-Derived Heterocyclic Amines by Sulphoraphene - an Isothiocyanate Isolated from Radish

Shishu,; Ak, Singla; Ip, Kaur

doi:10.1055/s-2003-37713

Cited by 25 publications

(19 citation statements)

References 10 publications

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“…Associated with the ability of SF to inhibit phase 1 enzymes is its ability to inhibit the formation of carcinogen-induced DNA adducts. In vitro antimutagenicity studies strongly suggest that SF is a potent inhibitor of the mutagenicity induced by heterocyclic amines (HCAs) [35]. Exposure to HCAs derived from cooked meat has been implicated in the etiology of certain human cancers including colon, prostate and breast cancer.…”

Section: Inhibition Of Phase 1 Enzymes and Dna Adductsmentioning

confidence: 99%

Molecular basis for chemoprevention by sulforaphane: a comprehensive review

Juge

Mithen

Τράκα

2007

Cell. Mol. Life Sci.

628

490

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The consumption of cruciferous vegetables has long been associated with a reduced risk in the occurrence of cancer at various sites, including the prostate, lung, breast and colon. This protective effect is attributed to isothiocyanates present in these vegetables, and sulforaphane (SF), present in broccoli, is by far the most extensively studied to uncover the mechanisms behind this chemoprotection. The major mechanism by which SF protects cells was traditionally thought to be through Nrf2-mediated induction of phase 2 detoxification enzymes that elevate cell defense against oxidative damage and promote the removal of carcinogens. However, it is becoming clear that there are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity. Moreover, these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.

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Section: Inhibition Of Phase 1 Enzymes and Dna Adductsmentioning

confidence: 99%

Molecular basis for chemoprevention by sulforaphane: a comprehensive review

Juge

Mithen

Τράκα

2007

Cell. Mol. Life Sci.

628

490

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“…Moreover, SFN was effective in eradicating H. pylori in human gastric xenografts implanted in nude mice (16). The mutagenicity of food-derived heterocyclic amines was inhibited by a SFN analog in the Ames Salmonella/reversion assay (17). SFN as well as its N-acetylcysteine conjugate administered during the postinitiation period effectively reduced azoxymethane-induced colonic aberrant crypt foci formation in rats (18).…”

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confidence: 99%

Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C

Singh

Herman-Antosiewicz

Singh

et al. 2004

Journal of Biological Chemistry

325

306

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Previously, we showed that sulforaphane (SFN), a naturally occurring cancer chemopreventive agent, effectively inhibits proliferation of PC-3 human prostate cancer cells by causing caspase-9-and caspase-8-mediated apoptosis. Here, we demonstrate that SFN treatment causes an irreversible arrest in the G 2 /M phase of the cell cycle. Cell cycle arrest induced by SFN was associated with a significant decrease in protein levels of cyclin B1, cell division cycle (Cdc) 25B, and Cdc25C, leading to accumulation of Tyr-15-phosphorylated (inactive) cyclin-dependent kinase 1. The SFN-induced decline in Cdc25C protein level was blocked in the presence of proteasome inhibitor lactacystin, but lactacystin did not confer protection against cell cycle arrest. Interestingly, SFN treatment also resulted in a rapid and sustained phosphorylation of Cdc25C at Ser-216, leading to its translocation from the nucleus to the cytoplasm because of increased binding with 14-3-3␤. Increased Ser-216 phosphorylation of Cdc25C upon treatment with SFN was the result of activation of checkpoint kinase 2 (Chk2), which was associated with Ser-1981 phosphorylation of ataxia telangiectasia-mutated, generation of reactive oxygen species, and Ser-139 phosphorylation of histone H2A.X, a sensitive marker for the presence of DNA double-strand breaks. Transient transfection of PC-3 cells with Chk2-specific small interfering RNA duplexes significantly attenuated SFN-induced G 2 /M arrest. HCT116 human colon cancer-derived Chk2 ؊/؊ cells were significantly more resistant to G 2 /M arrest by SFN compared with the wild type HCT116 cells. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in irreversible G 2 /M arrest by SFN. Activation of Chk2 in response to DNA damage is well documented, but the present study is the first published report to link Chk2 activation to cell cycle arrest by an isothiocyanate.Epidemiological studies have revealed an inverse correlation between the dietary intake of cruciferous vegetables and the risk for certain types of cancers, including prostate cancer (1-5). Laboratory studies indicate that the anticancer effect of cruciferous vegetables is caused by isothiocyanates that exist as thioglucoside conjugates (glucosinolates) in a variety of edible plants including broccoli, cabbage, watercress, and so forth (6 -9). Cruciferous vegetable-derived organic isothiocyanates are generated by hydrolytic cleavage of corresponding glucosinolates through catalytic mediation of myrosinases, which are released when the plant cells are damaged because of cutting or chewing (6 -9). Sulforaphane (SFN) 1 is one such isothiocyanate analog that has received a great deal of attention not only because it is present in high concentrations in certain varieties of broccoli but also because of its potent anticancer activity (10 -15). For example, oral administration of SFN (1-isothiocyanato-4-(methylsulfinyl)butane; CH 3 -SO-(CH 2 ) 4 -NϭCϭS)) caused a statistically significant reduction in 9,10-dimethyl-1,2-benzanthr...

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“…There are, nevertheless, many compounds in foods and beverages that have been shown to have beneficial effects on human health without significant associated toxicity. Such are, for example, resveratrol in red grapes (an oxidant and immunomodula ng proper es) [1336,1337]; antocyanins, lycopene and other carotenoids in red in red-and yellowcoloured vegetables (an oxidant proper es) [1338,1340]; sulphoraphane and indole-3-carbinol in cruciferous vegetables (an cancer effect) [1341], and others. All these fruits and vegetables are components of the normal human diet (or, at least, ought to be).…”

Section: S Snegov the Experiments Of Professor Bran Ng (1977)mentioning

confidence: 99%

DNA repair systems

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The gene c bases of diseases and condi ons associated with defec ve DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensi vity syndromes. The review analyses the basic molecular mechanisms underlying the rela vely rare monogenic diseases of DNA repair and management of genome integrity as well as the common mul factorial diseases and condi ons with late onset that are associated with increased levels of oxida ve stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumula on of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous ssues. The role of major DNA damageassociated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, re noblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limi ng the presence of damaged cells and cells with poten ally oncogenic transforma on in mul cellular organisms. Special a en on is paid to ageing as a natural phenomenon and an adap ve evolu onary mechanism, with a brief outline of 'successful ageing'. The differen al rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specifici es of DNA repair profile in some types of cells (terminally differen ated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replica ve ageing and the evolu onary processes on microand macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing gene c diversity in the course of individual life and on evolu onary scale and the phenomenology of ongoing molecular evolu on are extensively reviewed. Conflict of Interests:No poten al conflict of interest was disclosed by any of the authors. Types of DNA repair systemsIf you wish for peace, prepare for war.Publius Flavius Vege us Renatus, De Re Militari (circa 380 AD).DNA damage is a very broad term, encompassing many different types of lesions in DNA.Accordingly, DNA repair comprises many different types of pathways and mechanisms covering virtually every possible type of injury to the sequence or the structure of DNA.Accep ng Lewin's defini on of DNA damage "... any change that introduces a devia on from the usual double-helical structure" [1] , we may pre...

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Inhibition of Mutagenicity of Food-Derived Heterocyclic Amines by Sulphoraphene - an Isothiocyanate Isolated from Radish

Cited by 25 publications

References 10 publications

Molecular basis for chemoprevention by sulforaphane: a comprehensive review

Molecular basis for chemoprevention by sulforaphane: a comprehensive review

Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C

DNA repair systems

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