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      Cytotoxic Activity of Curcumin towards CCRF-CEM Leukemia Cells and Its Effect on DNA Damage

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          Abstract

          The cytotoxic activity of curcumin towards CCRF-CEM human T-cell leukemia cells was measured by the MTT assay. Tumor cells were more sensitive to the cytotoxic activity of curcumin or curcumin-Cu (II) compared to normal cells, and the IC 50 of curcumin towards CCRF-CEM cells was 8.68 µM, and that of curcumin-Cu (II) was 8.14 µM. The cell cycle distribution of curcumin-treated CCRF-CEM cells was analyzed by flow cytometry. DNA damage induced by oxidants such as curcumin-Cu (II) ions is considered as one of the main causes of cell inactivation. Therefore, we analyzed the effect of curcumin on DNA damage by agarose gel electrophoresis and atomic force microscopy (AFM). Gel electrophoresis analyses showed that curcumin or Cu (II) alone failed to cause DNA damage in pBR322 plasmid DNA as compared with the normal plasmid. However, DNA plasmids were mostly damaged after treatment with curcumin of different concentrations in the presence of Cu (II). Two forms were observed by means of AFM: closed circular plasmids and linear plasmids. DNA damage induced by a combination of curcumin and Cu (II) was also found by agarose gel electrophoresis, which was applied as control method to verify the results obtained by AFM.

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          Most cited references18

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          Curcumin: the story so far.

          Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.
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            Plant phenolic antioxidant and prooxidant activities: phenolics-induced oxidative damage mediated by metals in plants.

            Y Sakihama (2002)
            Plant phenolic compounds such as flavonoids and lignin precursors are important constituents of the human diet. These dietary phytophenolics have been recognized largely as beneficial antioxidants that can scavenge harmful active oxygen species including O(2)(.-), H(2)O(2), .OH, and (1)O(2). Here we review our current understanding of the antioxidant and prooxidant actions of phenolics in plant cells. In plant systems, phytophenolics can act as antioxidants by donating electrons to guaiacol-type peroxidases (GuPXs) for the detoxification of H(2)O(2) produced under stress conditions. As a result of such enzymatic as well as non-enzymatic antioxidant reactions, phenoxyl radicals are formed as the primary oxidized products. Until recently, phenoxyl radicals had been difficult to detect by static electron spin resonance (ESR) because they rapidly change to non-radical products. Application of Zn exerts spin-stabilizing effects on phenoxyl radicals that enables us to analyze the formation and decay kinetics of the radicals. The ESR signals of phenoxyl radicals are eliminated by monodehydroascorbate radical (MDA) reductase, suggesting that phenoxyl radicals, like the ascorbate radical, are enzymatically recycled to parent phenolics. Thus, phenolics in plant cells can form an antioxidant system equivalent to that of ascorbate. In contrast to their antioxidant activity, phytophenolics also have the potential to act as prooxidants under certain conditions. For example, flavonoids and dihydroxycinnamic acids can nick DNA via the production of radicals in the presence of Cu and O(2). Phenoxyl radicals can also initiate lipid peroxidation. Recently, Al, Zn, Ca, Mg and Cd have been found to stimulate phenoxyl radical-induced lipid peroxidation. We discuss the mechanism of phenoxyl radical prooxidant activity in terms of lifetime prolongation by spin-stabilizing agents.
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              Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells.

              Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration- and time-dependent manner. Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1. These data suggest that a non-toxic concentration of curcumin has a significant effect on the in vitro growth of HT-29 cells, specifically inhibits COX-2 expression, and may have value as a safe chemopreventive agent for colon cancer.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                Molecular Diversity Preservation International
                1420-3049
                17 December 2009
                December 2009
                : 14
                : 12
                : 5328-5338
                Affiliations
                [1 ]Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; E-Mails: kongyu820202@ 123456yahoo.com.cn (Y.K.); zygorl@ 123456vip.hl.cn (Y.Z.); lx20030135@ 123456yahoo.com.cn (X.L.); bao_doubao@ 123456yahoo.com.cn (N.W.); luliang20090320@ 123456yahoo.com.cn (L.L.); ylp2003@ 123456126.com (L.Y.)
                [2 ]Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China
                [3 ]Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China; E-Mail: maboshi99@ 123456yahoo.com.cn (W.M.)
                [4 ]Department of Pharmaceutical Biology, Institute of Pharmacy, University of Mainz, 55099 Mainz, Germany; E-Mail: t.efferth@ 123456dkfz.de (T.E.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: yujie_fu2002@ 123456yahoo.com ; Fax: +86-451-82190535.
                [†]

                These authors contributed equally to this work.

                Article
                molecules-14-05328
                10.3390/molecules14125328
                6255027
                20032896
                460c9d3e-b692-460f-b0de-67b1bf5cedf2
                © 2009 by the authors;

                licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 27 October 2009
                : 20 November 2009
                : 02 December 2009
                Categories
                Article

                curcumin,activity,cem,dna damage
                curcumin, activity, cem, dna damage

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