Oxy-radicals and cancer

Cerutti, Peter

doi:10.1016/s0140-6736(94)92832-0

Cited by 478 publications

(254 citation statements)

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“…The response of living systems to oxidative stress is of primary importance in understanding cellular defence and aging [12][13][14][15]. Disorders of normal oxidative metabolism, or damages due to oxidative stress, have also been proven to be key players in a broad spectrum of diseases, from neurodegenerative disorders, such as Alzheimer disease [16][17][18][19][20][21][22], to various kinds of cancer [23][24][25][26], diabetes [27][28][29], and atherosclerosis [30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Barelli

Canellini

Thadikkaran

et al. 2008

Proteomics Clinical Apps

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Protein oxidation mechanisms result in a wide array of modifications, from backbone cleavage or protein crosslinking to more subtle modifications such as side chain oxidations. Protein oxidation occurs as part of normal regulatory processes, as a defence mechanism against oxidative stress, or as a deleterious processes when antioxidant defences are overcome. Because blood is continually exposed to reactive oxygen and nitrogen species, blood proteomics should inherently adopt redox proteomic strategies. In this review, we recall the biochemical basis of protein oxidation, review the proteomic methodologies applied to analyse redox modifications, and highlight some physiological and in vitro responses to oxidative stress of various blood components.

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Section: Introductionmentioning

confidence: 99%

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Barelli

Canellini

Thadikkaran

et al. 2008

Proteomics Clinical Apps

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“…The increased enzymatic activities will protect cellular components from oxidative damage as the results of environmental oxidative insult or reactive metabolites, which can cause carcinogenesis (13)(14)(15). In fact, induction of QR1 in vitro has been used as a method to identify potential prostate cancer-preventive agents (16).…”

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confidence: 99%

Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol^,

et al. 2004

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Resveratrol has been shown to have chemopreventive, cardioprotective, and antiaging properties. Here, we report that resveratrol is a potent inhibitor of quinone reductase 2 (QR2) activity in vitro with a dissociation constant of 35 nM and show that it specifically binds to the deep active-site cleft of QR2 using high-resolution structural analysis. All three resveratrol hydroxyl groups form hydrogen bonds with amino acids from QR2, anchoring a flat resveratrol molecule in parallel with the isoalloxazine ring of FAD. The unique active-site pocket in QR2 could potentially bind other natural polyphenols such as flavonoids, as proven by the high affinity exhibited by quercetin toward QR2. K562 cells with QR2 expression suppressed by RNAi showed similar properties as resveratrol-treated cells in their resistance to quinone toxicity. Furthermore, the QR2 knockdown K562 cells exhibit increased antioxidant and detoxification enzyme expression and reduced proliferation rates. These observations could imply that the chemopreventive and cardioprotective properties of resveratrol are possibly the results of QR2 activity inhibition, which in turn, upregulates the expression of cellular antioxidant enzymes and cellular resistance to oxidative stress.Resveratrol (trans-3,4′,5-trihydroxystilbene) is a phyto-polyphenol that occurs in grapes and a variety of medicinal plants. Because of its abundance in grapes, it is present in significant amount in grape products such as grape juice and wines, particularly red wine (1). The revealing of resveratrol as a cancer chemopreventive agent in 1997 (2) sparked extensive research on its chemopreventive properties (3). Resveratrol has been tested on a variety of cancers in animal model studies. As in the case of the 1997 study, Jang et al. (2) demonstrated in a mouse model that resveratrol is effective in prevention of DMBA-(dimethylbenzanthracene) and TPA-(tetradecanoylphorbol-13-acetate) induced skin cancer. Application of 1, 5, 10, or 25 µM of resveratrol with TPA twice a week for 18 weeks reduced the number of skin tumors per mouse by 68, 81, 76, or 98%, respectively, and the percentage of mice with tumors was lowered by 50, 63. 63, or 88%. In mouse models of colon cancer and small intestinal cancer, resveratrol prevents cancer formation with 100 and 70% efficacy, respectively (4, 5). † This work was supported in part by National Institute of Health Grant R21 CA104424. ‡ The atomic coordinates and structure factors (PDB code 1SG0) NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResveratrol has been suggested to block the multistep process of carcinogenesis, namely, tumor initiation, promotion, and progression (3). Despite extensive investigation, no clear molecular basis for the actions of resveratrol has emerged. A variety of hypotheses have been proposed to explain its functions: antioxidant effects, proapoptotic effects, cell-cycle regulation, inhibition of protein kinases, regulation of NFκB and Iκ3, and modulation of estrogen effects (3, 6). ...

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“…Free radicals induced LP and the role of free radicals in carcinogenesis is also well known (Cerutti, 1994). LP index, greatly enhanced in animals fed with DAB, was not modified by CIM, consequently liver cytotoxicity should be ascribed to oxidative stress and it was here demonstrated by the persistent increase in GST activity.…”

Section: Discussionmentioning

confidence: 55%

“…Accumulation of damage alters gene function and clonal expansion of mutated cells (Cerutti, 1994). During drug metabolism, generated reactive oxygen species (ROS) play a key role in several stages of carcinogenesis (Halliwell, 1999;Caballero et al, 2001).…”

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confidence: 99%

Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation

et al. 2002

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Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other metabolic alterations provoked by the carcinogen pdimethylaminoazobenzene. A group of male CF1 mice received a standard laboratory diet and another group was placed on dietary p-dimethylaminoazobenzene (0.5% w w 71 ). After 40 days of treatment, animals of both groups received pdimethylaminoazobenzene and two weekly doses of cimetidine (120 mg kg 71 , i.p.) during a following period of 35 days. Cimetidine prevented and reversed d-aminolevulinate synthetase induction and cytochrome P450 enhancement provoked by p-dimethylaminoazobenzene. However, cimetidine did not restore haem oxygenase activity decreased by p-dimethylaminoazobenzene. Enhancement in glutathione S-transferase activity provoked by p-dimethylaminoazobenzene, persisted in those animals then treated with cimetidine. This drug did not modify either increased lipid peroxidation or diminution of the natural antioxidant defence system (inferred by catalase activity) induced by p-dimethylaminoazobenzene. In conclusion, although cimetidine treatment partially prevented and reversed cytochrome P450 induction, and alteration on haem metabolism provoked by p-dimethylaminoazobenzene AB, it did not reverse liver damage or lipid peroxidation. These results further support our hypothesis on the necessary existence of a multiple biochemical pathway disturbance for the onset of hepatocarcinogenesis initiation.

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Oxy-radicals and cancer

Cited by 478 publications

References 0 publications

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol^,

Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation

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Oxy-radicals and cancer

Cited by 478 publications

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Oxidation of proteins: Basic principles and perspectives for blood proteomics

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol,

Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation

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Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol^,