Oxidant stress and carcinogenesis

Cerutti, Peter

doi:10.1111/j.1365-2362.1991.tb01350.x

Cited by 201 publications

(84 citation statements)

References 21 publications

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“…16 O 2 ], are very labile and have short half-lives. Under normal physiological conditions, there is a balance between oxidative and reductive (redox) homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Expression of heavy subunit of γ‐glutamylcysteine synthetase (γ‐GCSh) in human colorectal carcinoma

Tatebe

Unate

Sinicrope

et al. 2001

Intl Journal of Cancer

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Gamma-glutamylcysteine synthetase (␥-GCS) is a heterodimer consisting of heavy (␥-GCSh) and light (␥-GCSl) subunits. ␥-GCS catalyzes the rate-limiting de novo biosynthesis of glutathione (GSH), an abundant physiological antioxidant that plays important roles for regulating oxidative stress. Expression of ␥-GCSh and ␥-GCSl are sensitive to oxidative stress. To investigate whether expression of ␥-GCS is correlated with tumor progression, we used immunohistochemical approaches to examine 16 human colorectal adenomas and resected 57 carcinomas from untreated patients. In adjacent normal colorectal epithelium, levels of ␥-GCSh expression were low. Strong cytoplasmic staining for ␥-GCSh was detected in 3 (18.8%) adenoma and 48 (84.2%) carcinomas. The frequency of ␥-GCSh expression in carcinoma was significantly higher than in adenoma (p<0.0001). We used RNase protation assay and Western blot to determine levels of ␥-GCSh mRNA and protein from 10 pairs of matched carcinomas with adjacent normal controls. Elevated expression of both ␥-GCSh mRNA and protein were found in 6 cases, suggesting that transcriptional and/or posttranscriptional regulation play an important role in the upregulation of ␥-GCS during colorectal carcinogenesis. We also examined the expression of another redox-regulated gene, multidrug resistance protein 1 (MRP1). Strong staining for MRP1 was detected in 1 (6.3%) adenoma and 40 (70.2%) carcinomas. The frequency of MRP1 expression in carcinoma was significantly higher than in adenoma ( p<0.0001). Nuclear p53 expression was detected in 30 (52.6%) of carcinomas. There is a significant correlation between ␥-GCSh and MRP1 expression (p‫)310.0؍‬ but not between ␥-GCSh and p53. Since ␥-GCS is a sensor of oxidative stress, these results are consistent with the notion that oxidative stress is associated with colorectal tumor progression. © 2002 Wiley-Liss, Inc. Key words: ␥-GCSh; MRP1; colorectal neoplasmGlutathione (GSH) plays an important role in regulating intracellular redox conditions. Biosynthesis of GSH involves 2 enzymatic reactions: the first reaction involves the synthesis of glutamylcysteine through ␥-peptide bond formation between glutamate and cysteine and is catalyzed by the rate-limiting enzyme gamma-glutamylcysteine synthetase. 1 The second reaction is catalyzed by GSH synthetase, which conjugates glycine to glutamylcysteine. The mammalian ␥-GCS holoenzyme is a heterodimer that consists of a 73 kDa heavy subunit (␥-GCSh) and a 28 kDa light subunit (␥-GCSl). [2][3][4][5] The steady-state levels of ␥-GCSh and ␥-GCSl mRNA are increased in cultured cells exposed to prooxidants (␤-naphthoflavone, menadione, tert-butylhydorquinone and pyrrolidine dithiocarbamate, 6,7 ), antitumor agents (cisplatin, 8 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3 nitrosourea 9 ), cytokines (interleukin 1␤ 10 ), etc. These cytotoxic agents are known to generate reactive oxygen species (ROS) and exert various degrees of oxidative stress to the cells. In all cases, induction of ␥-GCS is accompanied by the...

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“…16 O 2 ], are very labile and have short half-lives. Under normal physiological conditions, there is a balance between oxidative and reductive (redox) homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Expression of heavy subunit of γ‐glutamylcysteine synthetase (γ‐GCSh) in human colorectal carcinoma

Tatebe

Unate

Sinicrope

et al. 2001

Intl Journal of Cancer

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“…Reactive oxygen species, generated as byproducts of biological reactions or from exogenous factors, 22) are well known to play important roles in the pathogenesis of various diseases, such as neurodegenerative disorders, cancer, cardiovascular diseases, atherosclerosis and inflammation. 23) NO is a widespread intra-and intercellular messenger and cytotoxin.…”

Section: Discussionmentioning

confidence: 99%

Increase in the Free Radical Scavenging Activity of Ginseng by Heat-Processing

Kang

Kim

Pyo

et al. 2006

Biological & Pharmaceutical Bulletin

140

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Reactive oxygen metabolites, including free radicals such as nitric oxide (NO), superoxide anion (O 2 Ϫ ), hydroxyl ( · OH) radicals and peroxynitrite (ONOO Ϫ ), are toxic and play an important role in tissue injury.1,2) O 2 Ϫ reacts rapidly with NO to produce the more toxic ONOO Ϫ . In addition, ONOO Ϫ and its decomposition product, · OH, contribute to antioxidant depletion, alterations of protein structure and oxidative damage observed in human diseases. [3][4][5] Thus, it is important to find safe and effective scavengers of these oxygen radicals for prevention and treatment of oxidative stress-related diseases.Panax ginseng C. A. MEYER is one of the most widely used herbal medicines in the Orient. It has a wide range of pharmacological and physiological actions, such as antiaging, immunoenhancement, antistress and antitumor. [6][7][8] Of the two kinds of ginseng, white ginseng (WG), is air-dried ginseng, and red ginseng (RG) is produced by steaming raw ginseng at 98-100°C for 2-3 h. RG is reportedly more pharmacologically active than WG. These improved biological activities of ginseng result from changes in the chemical constituents that occur during steaming treatment. Ginseng saponins, referred to as ginsenosides, are believed to play a pharmacologically important role. Several investigators have reported new ginsenosides from RG that are not usually found in WG.9,10) Recently, a method which can enhance the yield of these RG specific ginsenosides by steaming ginseng at a temperature higher than RG has been developed.11) This heat-processed ginseng, termed sun ginseng (SG), has been reported to have more potent pharmacological activities, such as vasorelaxation, antioxidant and antitumor activities.12,13) In our preliminary study, SG also showed better NO-scavenging activity than conventional WG and RG. However, almost all ginsenosides had no effects on radical scavenging activity (data not shown). It is insufficient to explain the various pharmacological effects of ginseng with only ginsenosides, especially antioxidant activity related to radical scavenging. Therefore, in this study, we focused on phenolic compounds in ginseng, such as maltol, salicylic acid, vanillic acid and p-coumaric acid, known as principal antioxidant components of ginseng, to investigate the radical scavenging activity of SG. We examined the NO, O 2 Ϫ , ONOO Ϫ and · OHscavenging activities of WG, RG and SG. Furthermore, we also studied the radical scavenging activities of maltol, salicylic acid, vanillic acid and p-coumaric acid and the contents of these 4 phenolic compounds in WG, RG and SG. MATERIALS AND METHODSReagents Salicylic acid, p-coumaric acid, vanillic acid, maltol, sodium nitroprusside (SNP), nitro blue tetrazolium (NBT), b-nicotineamide adenine dinucleotide disodium salt reduced form (b-NADH), DL-penicillamine and L(ϩ)-ascorbic acid were obtained from Wako Pure Chemical Industries Ltd. (Osaka, Japan). Bis(trimethylsilyl)trifluoroacetamide plus 1% trimethylchlorosilane, n-eicosane, phenazine methosulfate (PMS), 3-morpho...

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“…Reactive oxygen species (ROS), including the free radicals superoxide anion ($O À 2 ), hydroxyl radicals ($OH), and singlet oxygen ( 1 O 2 ) and non-free-radical species, such as hydrogen peroxide (H 2 O 2 ), are various forms of activated oxygen resulting from oxidative biological reactions or exogenous factors [1,2]. ROS have been shown to exert beneficial as well as deleterious actions.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Antioxidant and Free Radical Scavenging Activity of Nardostachys jatamansi DC.

Sharma

Singh

2012

Journal of Acupuncture and Meridian Studies

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In this study, the antioxidative potential of a hydroalcoholic extract of Nardostachys jatamansi (NJE) rhizomes was evaluated by various antioxidant assays, including antioxidant capacity by the phosphomolybdenum method, total antioxidant activity in linoleic acid emulsion systems, 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide, hydroxyl radicals, nitric oxide (NO) scavenging, metal chelating and reducing power activity. These various antioxidant activities were compared with standard antioxidants such as butylated hydroxytoluene, tocopherol, catechin, and L-ascorbic acid. Total phenolic and flavonoid content of NJE was also determined by a colorimetric method. The extract exhibited high reduction capability and powerful free radical scavenging, especially against DPPH and superoxide anions as well as a moderate effect on NO. Moreover, the peroxidation inhibiting activity of NJE was demonstrated in the linoleic acid emulsion system. The results obtained in the present study clearly established the antioxidative potency of NJE, which may account for some of the medical claims attributed to this plant.

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Oxidant stress and carcinogenesis

Cited by 201 publications

References 21 publications

Expression of heavy subunit of γ‐glutamylcysteine synthetase (γ‐GCSh) in human colorectal carcinoma

Expression of heavy subunit of γ‐glutamylcysteine synthetase (γ‐GCSh) in human colorectal carcinoma

Increase in the Free Radical Scavenging Activity of Ginseng by Heat-Processing

In Vitro Antioxidant and Free Radical Scavenging Activity of Nardostachys jatamansi DC.

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