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      Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells

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          Abstract

          Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50  μ g mL −1 EEP and 100 ng mL −1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68–66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.

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          Dietary agents in cancer prevention: flavonoids and isoflavonoids.

          Flavones and isoflavones may play a prominent role in cancer prevention since these compounds are found in numerous plants that are associated with reduced cancer rates. This article reviews recent epidemiological and animal data on isoflavones and flavones and their role in cancer prevention. It covers aspects of the bioavailability of these dietary constituents and explores their mechanism of action. Human epidemiology data comes primarily from studies in which foods rich in isoflavones or flavones are associated with cancer rates. This approach has been particularly useful with isoflavones because of their abundance in specific foods, including soy foods. The bioavailability of flavones and isoflavones has been shown to be influenced by their chemical form in foods (generally glycoside conjugates), their hydrophobicity, susceptibility to degradation, the microbial flora of the consumer, and the food matrix. Some information is available on how these factors influence isoflavone bioavailability, but the information on flavones is more limited. Many mechanisms of action have been identified for isoflavone/flavone prevention of cancer, including estrogenic/antiestrogenic activity, antiproliferation, induction of cell-cycle arrest and apoptosis, prevention of oxidation, induction of detoxification enzymes, regulation of the host immune system, and changes in cellular signaling. It is expected that some combination of these mechanisms will be found to be responsible for cancer prevention by these compounds. Compelling data suggest that flavones and isoflavones contribute to cancer prevention; however, further investigations will be required to clarify the nature of the impact and interactions between these bioactive constituents and other dietary components.
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            Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy.

            Apo2 ligand or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is one of several members of the TNF gene superfamily that induce apoptosis through engagement of death receptors. Apo2L/TRAIL is unusual as compared to any other cytokine as it interacts with a complex system of receptors: two pro-apoptotic death receptors and three anti-apoptotic decoys. This protein has generated tremendous excitement as a potential tumor-specific cancer therapeutic because, as a stable soluble trimer, it selectively induces apoptosis in many transformed cells but not in normal cells. Transcriptional activation of Apo2L/TRAIL by interferons (IFNs) through specific regulatory elements in its promoter, and possibly by a number of other cytokines, reveals its possible involvement in the activation of natural killer cells, cytotoxic T lymphocytes, and dendritic cells. In this review, we focus on the apoptosis signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date about the physiological role of this ligand and the potential for its application to cancer therapy.
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              Analysis of the polyphenolic fraction of propolis from different sources by liquid chromatography-tandem mass spectrometry.

              A reverse phase LC-DAD-MS method for quantification of phenolic acids and flavonoids in propolis raw materials was developed. The propolis samples from different geographical areas were extracted with ethanol for 2h at 70 degrees C and the resulting solutions analyzed on a 5 microm C18 symmetry 250 mm x 4.6mm column. The separation was performed by means of a linear gradient elution and DAD and MS data were acquired in the 200-450 nm and 100-1000 Da range, respectively. The identity of most of the compounds was assessed by comparing their chromatographic and UV behaviour with that of authentic standards. When the standards were not available, the identity was achieved by means of chromatographic and on-line UV data combined with mass spectrometry. European, Chinese and Argentinean propolis are characterized by the presence of phenolic acids and flavonoids and the most abundant were chrysin (2-4%), pinocembrin (2-4%), pinobanksin-acetate (1.6-3%) and galangin (1-2%). Some Brazilian propolis contains mainly artepillin C, different caffeoyl quinic acids and some flavonoids. When considering the total flavonoid content as quality index, we suggest that propolis with a content less than 11% should be considered of low quality, whereas propolis with a content of 11-14%, 14-17% or >17% should be classified as propolis of acceptable, good and high quality, respectively. The reported LC-DAD-MS analysis method may be applied for the phytochemical screening of raw propolis and its commercial formulations.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2011
                7 June 2011
                7 June 2011
                : 2011
                : 535172
                Affiliations
                1Chair and Department of Microbiology and Immunology, Jordana 19, 41808 Zabrze, Poland
                2Chair and Department of Urology, 3-go Maja 13, 41 800 Zabrze, Medical University of Silesia in Katowice, Poland
                Author notes
                Article
                nep180
                10.1093/ecam/nep180
                3138536
                19892808
                4e9b15bc-97df-4dce-8945-ddffaf5cb6c8
                Copyright © 2011 Ewelina Szliszka et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 February 2009
                : 6 October 2009
                Categories
                Original Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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