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M. F. Ullah Aamir Ahmad Husain Y. Khan H. Zubair Fazlul H. Sarkar S. M. Hadi 《Cell biochemistry and biophysics》2013,67(2):431-438
Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells. 相似文献
133.
Steroid hormone mimics: molecular mechanisms of cell growth and apoptosis in normal and malignant mammary epithelial cells 总被引:2,自引:0,他引:2
Anti-estrogen (anti-E2) therapy with E2 receptor antagonists has a significant benefit in women with breast cancer, but it may also increase the risk for developing hormone-independent breast cancer for which there is no therapy similar to that used in hormone-dependent breast cancer. Therefore, there is a significant interest in the development of compounds that may provide therapeutic benefit for hormone-independent breast cancer without untoward risks and adverse effects. The estrogen receptor (ER) modulators with both agonistic as well as antagonistic properties may, thus, be exploited for the development of the next generation of compounds for the prevention and/or treatment of breast cancer. In this article, we have discussed the clinical indications, risks, benefits and mechanisms of action of ER modulators and related compounds, particularly indole-3-carbinol (I3C), which may open new avenues for the prevention and/or treatment of breast cancer. 相似文献
134.
Extraction, thin-layer chromatography, and gas chromatography–mass spectrometry of leaf surface waxes of Momordica charantia L. (Cucurbitaceae) revealed that 20 n-alkanes between n-C15 and n-C36, except n-C34 and n-C35, commonly occur in young, mature, and senescent stages. Hentriacontane, hentriacontane, and hexatriacontane were the predominant compounds in young, mature, and senescent leaves, respectively. The cuticular alkanes from young, mature, and senescent leaves attracted the female insect, Epilachna dodecastigma (Wied.), at 25–400, 25–400, and 100–400 μg concentrations, respectively, whereas the mixtures of synthetic alkanes mimicking cuticular alkanes of young, mature, and senescent leaves showed attraction at 100–400, 100–400, and 200–400 μg concentrations, respectively, in Y-shaped glass tube olfactometer bioassay. The difference in insect attraction is probably due to the absence of branched-chain alkanes in the synthetic mixtures. Individual synthetic heptacosane, nonacosane, and hentriacontane at 28.19–56.90, 32.04–64.08, and 60.44–120.88 μg, respectively, elicited attraction of the insect. A synthetic blend of 4.82, 4.91, 5.71, 6.74, 56.39, 7.94, 62.42, 120.88, and 36.33 μg of nonadecane, eicosane, heneicosane, pentacosane, heptacosane, octacosane, nonacosane, hentriacontane, and tritriacontane, respectively, was most attractive to the insect. 相似文献
135.
Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics 总被引:1,自引:0,他引:1
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Unlike human serum albumin (HSA), dog serum albumin (DSA) does not possess the characteristics of the specific first binding site for Cu(II). In DSA, the important histidine residue in the third position, responsible for the Cu(II)-binding specificity in HSA, is replaced by a tyrosine residue. In order to study the influence of the tyrosine residue in the third position of DSA, a simple model of the NH2-terminal native sequence tripeptide of DSA, glycylglycyl-L-tyrosine-N-methylamide (GGTNMA) was synthesized and its Cu(II)-binding properties studied by analytical potentiometry, spectrophotometry, CD, and NMR spectroscopy. The species analysis indicated the existence of five mono-complexes at different protonation states: MHA, MA, MH-1A, MH-2A, MH-3A, and only one bis-complex MH-2A-2. The complexing ability of GGTNMA to Cu(II) was found to be weaker than that of the Cu(II) binding peptide models of HSA. The visible absorption spectra of Cu(II)-GGTNMA complexes are similar to those observed in the case of DSA-Cu(II) complexes. The weaker binding and the spectral properties of Cu(II)-GGTNMA complexes are consistent with less specific Cu(II)-binding properties of the peptide of this sequence similar to what was noted with DSA. CD results are in excellent agreement with species analysis and visible spectra where it is clearly evident that Cu(II) binds to GGTNMA starting from the alpha-NH2 group and step by step to deprotonated amide nitrogens as the pH is raised. The absence of any charge transfer band around 400 nm strongly indicates that Cu(II) does not bind to the phenolate group. Furthermore, NMR results are consistent with the noninvolvement of the tyrosine residue of GGTNMA in Cu(II) complexation. Thus, it is clear that the low Cu(II)-binding affinity of DSA is due to the genetic substitution of tyrosine for histidine at the NH2-terminal region of the protein. 相似文献