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      Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells Translated title: Acción anti-proliferativa de silibinina sobre el cáncer adenomatoso de colon humano las células HT-29

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          Abstract

          Background: Silibinin a flavonoid from milk thistle (Silybum marianum) exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml) for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78%) was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells) values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008), Cancer Letters, 269: 352-62).

          Translated abstract

          Antecedentes: Silibinina un flavonoide a partir de la leche de cardo mariano (Silybum marianum) exhiben una variedad de acciones farmacológicas, incluyendo actividades anti-proliferativos y apoptóticos contra varios tipos de cánceres en animales intactos y líneas celulares de cáncer. En el presente estudio, se estudió el efecto de silibinina en células humanas de cáncer de colon HT-29. Método: Las incubaciones de las células con diferentes concentraciones silibinin (0,783-1.600 μg/ml) para 24, 48 o 72 horas mostró un descenso progresivo de la viabilidad celular. Resultados: La pérdida de la viabilidad celular fue de tiempo de inhibición dependiente y óptima de crecimiento de las células (78%) se observó a las 72 horas. Bajo microscopio invertido, las células muertas fueron vistos como los agregados de células. IC50 (concentración de silibinina matar a las células 50%) los valores fueron 180, 110 y 40 μg/ml a las 24, 48 y 72 horas, respectivamente. Conclusión: Estos resultados volver a hacer cumplir la potenciales contra el cáncer de silibinina, como se informó anteriormente para varias otras líneas celulares de cáncer (Ramasamy y Agarwal (2008), Cancer Letters, 269: 352-62).

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          Milk thistle (Silybum marianum) for the therapy of liver disease.

          Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.
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            Multitargeted therapy of cancer by silymarin.

            Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anti-cancer activities, and studies on human clinical trials.
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              Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties.

              Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. We have shown that several of these compounds are able to bind both DNA and Cu(II) forming a ternary complex. A redox reaction of the polyphenols and Cu(II) in the ternary complex may occur leading to the reduction of Cu(II) to Cu(I), whose reoxidation generates a variety of reactive oxygen species (ROS). We have further confirmed that the polyphenol-Cu(II) system is indeed capable of causing DNA degradation in cells such as lymphocytes. We have also shown that polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. Neocuproine (a Cu(I) sequestering agent) inhibits such DNA degradation. It also inhibits the oxidative stress generated in lymphocytes indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and polyphenols to generate ROS. Thus, our results are in support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper possibly chromatin bound copper and the consequent prooxidant action.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                nh
                Nutrición Hospitalaria
                Nutr. Hosp.
                Grupo Arán (Madrid, Madrid, Spain )
                0212-1611
                1699-5198
                February 2014
                : 29
                : 2
                : 388-392
                Affiliations
                [03] Chandigarh orgnamePostgraduate Institute of Medical Education and Research orgdiv1Department of Experimental Medicine and Biotechnology
                [01] orgnamePostgraduate Institute of Medical Education and Research orgdiv1Department of Pharmacology
                [04] Chandigarh orgnamePanjab University orgdiv1Department of Biophysics
                [02] New Delhi orgnameJamia Hamdard orgdiv1Faculty of Pharmacy
                Article
                S0212-16112014000200021
                10.3305/nh.2014.29.2.7080
                24528358
                2b394c8d-0658-4685-aa56-12575f64e85d

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 03 October 2013
                : 25 September 2013
                : 05 November 2013
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 19, Pages: 5
                Product

                SciELO Spain


                Cáncer de colon,HT-29,Proliferación,Silibinin,Colon cancer,Proliferation

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