Seleno-organic compounds and the therapy of hydroperoxide-linked pathological conditions

Parnham, Michael J.; Graf, Erich Otto

doi:10.1016/0006-2952(87)90617-4

Cited by 166 publications

(45 citation statements)

References 51 publications

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“…Oxidation of DFH by ROS yields a fluorescent species that can be detected by confocal microscopy. Although there is uncertainty over the specific oxidants that oxidize DFH in cells, it has been well documented that DFH is an important tool to indicate oxidations in cells and is one of a very few markers available for measuring intracellular ROS levels in live cells (32)(33)(34)(35) To determine whether ROS, specifically peroxides, are involved in the pathway of MnSOD up-regulation of MMP-2, Mn40 cells, the cells with highest MMP-2 activity, were treated with ebselen, a well established synthetic selenium-containing compound with GPx mimetic properties (36,37). This treatment dramatically suppressed DFH fluorescence at concentrations of 50 and 100 M. Correspondingly, a marked suppression of MMP-2 activation was also seen with these two dosages.…”

Section: Discussionmentioning

confidence: 99%

Activation of Matrix Metalloproteinase-2 by Overexpression of Manganese Superoxide Dismutase in Human Breast Cancer MCF-7 Cells Involves Reactive Oxygen Species

Zhang¹,

Zhao²,

Venkataraman³

et al. 2002

Journal of Biological Chemistry

171

110

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Cancer metastasis is a multistep process that includes invasion of cancer cells into blood vessels, traveling of these cells in the circulation system, and proliferation and eventual formation of a metastatic tumor at distal tissues. Among these steps, the first step of cancer cell invasion is a critical point for cancer metastasis. A current hypothesis proposes that remodeling of the extracellular matrix is a required process for cancer cell invasion (1, 2).The process of extracellular matrix remodeling happens in both normal physiological conditions and pathological diseases such as cancer invasion. Cancer invasion is a disordered and uncontrolled behavior that usually involves the interaction of tumor cells and their surrounding stromal cells, leading to the loss of matrix function and a compromised matrix boundary. Although several classes of proteases have been suggested in extracellular matrix remodeling, previous studies have demonstrated that the activation of zinc-dependent matrix metalloproteinases (MMPs) 1 was the primary response for the degradation of components of the extracellular matrix (3, 4).There are at least 15 members in the MMP family. MMP-2 (also called gelatinase A-type IV collagenase) and MMP-9 (geletinase B-type IV collagenase), two members of the MMP family, were postulated to play a critical role in tumor invasion. Lotta et al. have shown that the activities of MMP-2 and MMP-9 were higher in human breast cancer than the premalignant or normal breast tissue (1). In addition, in an experimental metastatic model, Stetler-Stevenson (5) has concluded that the protein level and activity of both enzymes were correlated with the metastatic potential of tumor cells.MMPs share similar mechanisms of activation and protease function. The regulation of MMP activation occurs at both mRNA and/or protein levels. For example, transforming growth factor-␤1 increases progelatinase mRNA levels in human fibroblasts (6). In addition, most MMPs are secreted as zymogens upon translation. Post-translational modification is required for MMP activation to acquire the proteolytic function.Previously, oxidation and oxidative stress have been implicated in the regulation of MMP activation. Increases in MMP-2 mRNA level and enzymatic activity were seen following xanthine/xanthine oxidase (X/XO) treatment (7) and ionizing radiation (8). It is well known that both the X/XO system and radiation produce reactive oxygen species (ROS) such as superoxide radicals and hydrogen peroxide. In fact, hydrogen perox-* This work was supported by NCI, National Institutes of Health (NIH), Grants P01 CA 66081 and CA84462, Public Health Service Grants AG 12350 and AG 14687, and NIDDK, NIH, Grant 51612. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.¶ To whom correspondence should be addressed: Free Radical and Radiation Biology, Dept. of Radiation Oncology,...

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Section: Discussionmentioning

confidence: 99%

Activation of Matrix Metalloproteinase-2 by Overexpression of Manganese Superoxide Dismutase in Human Breast Cancer MCF-7 Cells Involves Reactive Oxygen Species

Zhang¹,

Zhao²,

Venkataraman³

et al. 2002

Journal of Biological Chemistry

171

110

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“…Ebselen [2-phenyl-1,2-benzoisoselenazol-3(2H)-one] has been known as a mimetic of glutathione peroxidase (GPx), able to interact with active oxygen species present in living cells. [3][4][5][6] However, its use under nonenzymic conditions as a catalyst for hydrogen peroxide oxidation of thiols to disulfides gave poor results. Recently, Back et al 7,8 have demonstrated the exceptional glutathione peroxidase-like activity of the simple bis (3-hydroxypropyl) selenide and the unexpected role of its oxidation product, spirodioxaselenanone, as an intermediate in the catalytic redox cycle for GPx.…”

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confidence: 99%

Synthesis of Water-Soluble Vinyl Selenides and Their High Glutathione Peroxidase (GPx)-Like Antioxidant Activity

et al. 2013

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A convenient procedure for the synthesis of novel bis-(1-hydroxymethyl-2-halo-3-hydroxy-1-propylene) selenides has been developed. On oxidation these compounds form novel seleno-spiro compounds and their glutathione peroxidase mimetic activity has been studied. They promote the hydrogen peroxide oxidation of phenylmethanethiol to the corresponding disulfide via a catalytic cycle.Key words: alkynes, selenium, oxidation, spiro compounds, diols Glutathione peroxidase (GPx) is a selenoenzyme that protects cells by catalyzing the reduction of peroxides with the stoichiometric reductant glutathione. 1The enzyme catalytic site includes a selenocysteine residue in which the selenium undergoes a redox cycle involving the selenolate anion as the active form, which reduces hydroperoxides. The selenol is first oxidized to a selenenic acid EnzSeOH, which reacts with reduced glutathione GSH to form the selenyl sulfide EnzSeSG. A second glutathione then regenerates the active form of the enzyme by attacking the EnzSeSG to form the oxidized glutathione GSSG. The overall catalytic cycle is depicted in Figure 1. Ebselen [2-phenyl-1,2-benzoisoselenazol-3(2H)-one] has been known as a mimetic of glutathione peroxidase (GPx), able to interact with active oxygen species present in living cells. [3][4][5][6] However, its use under nonenzymic conditions as a catalyst for hydrogen peroxide oxidation of thiols to disulfides gave poor results. Recently, Back et al. 7,8 have demonstrated the exceptional glutathione peroxidase-like activity of the simple bis(3-hydroxypropyl) selenide and the unexpected role of its oxidation product, spirodioxaselenanone, as an intermediate in the catalytic redox cycle for GPx.In view of the known role of organoselenium compounds in biological systems, [9][10][11][12] in addition to their unique characteristics in organic synthesis, 13 the design and synthesis of novel organoselenium compounds with potential biological activity constitutes an ongoing challenge. Recently, we have found that in situ prepared selenium dichloride, readily obtained from elemental selenium and sulfuryl chloride, 14 undergoes smooth 1,2-addition to the triple bond of various propargylic alcohols resulting in the formation of symmetrical (Z,Z)-bis(1-hydroxymethyl-2-chlorovinyl) selenides 1 in high yields and in completely regio-and stereospecific manner (Scheme 1). 15,16Of special mechanistic interest is the observed syn-addition and anti-Markovnikov orientation.Scheme 1 Regio-and stereospecific synthesis of functionalized divinyl selenides Inspired by the above findings, we applied our regio-and stereospecific SeCl 2 addition protocol in the planned preparation of novel GPx-mimetics of spirodioxaselenurane type. 8Those divinyl selenides formed by syn-addition of SeCl 2 to the triple bond, which do not bear a vicinal hydrogen capable of cis elimination, gave stable selenoxides 2a,b and selenone 3 in good yield upon oxidation with tert-butyl hydroperoxide or with 2 equivalents of MCPBA, respectively (Scheme 2). The divinyl s...

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“…Recently, simple seleno-organic compounds were shown to mimic in vitro the enzymic activity of glutathione peroxidase, an important system of cell defence against oxidative stress (Parnham & Graf, 1987;Gfinzler, Steffens & Grossman, 1982). Such molecules are able to convert hydroperoxides into alcohols with their selenium-containing active centre.…”

Section: Commentmentioning

confidence: 99%

Structure of bis(2-amino-5-benzoylphenyl) diselenide

Warin¹,

Abdelhalim²,

Baert³

et al. 1993

Acta Crystallogr C

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Seleno-organic compounds and the therapy of hydroperoxide-linked pathological conditions

Cited by 166 publications

References 51 publications

Activation of Matrix Metalloproteinase-2 by Overexpression of Manganese Superoxide Dismutase in Human Breast Cancer MCF-7 Cells Involves Reactive Oxygen Species

Activation of Matrix Metalloproteinase-2 by Overexpression of Manganese Superoxide Dismutase in Human Breast Cancer MCF-7 Cells Involves Reactive Oxygen Species

Synthesis of Water-Soluble Vinyl Selenides and Their High Glutathione Peroxidase (GPx)-Like Antioxidant Activity

Structure of bis(2-amino-5-benzoylphenyl) diselenide

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