18
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Global estimates of cancer prevalence for 27 sites in the adult population in 2008.

          Recent estimates of global cancer incidence and survival were used to update previous figures of limited duration prevalence to the year 2008. The number of patients with cancer diagnosed between 2004 and 2008 who were still alive at the end of 2008 in the adult population is described by world region, country and the human development index. The 5-year global cancer prevalence is estimated to be 28.8 million in 2008. Close to half of the prevalence burden is in areas of very high human development that comprise only one-sixth of the world's population. Breast cancer continues to be the most prevalent cancer in the vast majority of countries globally; cervix cancer is the most prevalent cancer in much of Sub-Saharan Africa and Southern Asia and prostate cancer dominates in North America, Oceania and Northern and Western Europe. Stomach cancer is the most prevalent cancer in Eastern Asia (including China); oral cancer ranks as the most prevalent cancer in Indian men and Kaposi sarcoma has the highest 5-year prevalence among men in 11 countries in Sub-Saharan Africa. The methods used to estimate point prevalence appears to give reasonable results at the global level. The figures highlight the need for long-term care targeted at managing patients with certain very frequently diagnosed cancer forms. To be of greater relevance to cancer planning, the estimation of other time-based measures of global prevalence is warranted. Copyright © 2012 UICC.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            IAP family proteins--suppressors of apoptosis.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization.

              NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD. Copyright 2010 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2014
                27 September 2014
                : 8
                : 1629-1647
                Affiliations
                [1 ]Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [2 ]Medical Research Centre, Jazan University, Jazan, Saudi Arabia
                [3 ]Department of Molecular Medicine, Faculty of Medicine University of Malaya, Kuala Lumpur, Malaysia
                [4 ]Epigenetics Lab, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
                [5 ]Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [6 ]School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia
                [7 ]Department of Bioproduct Research and Innovation, Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, Johor, Malaysia
                [8 ]Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia
                [9 ]Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia
                Author notes
                Correspondence: Najihah Mohd Hashim, Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia, Tel +60 1 2327 9594, Fax +60 3 7967 4964, Email najihahmh@ 123456um.edu.my
                Mohamed Yousif Ibrahim, Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia, Tel +60 1 7337 9596, Fax +60 3 7967 4964, Email al_omdah2003@ 123456hotmail.com
                Article
                dddt-8-1629
                10.2147/DDDT.S66105
                4189707
                25302018
                a5cba284-66f7-4b16-a9d1-e9c1055f5b44
                © 2014 Ibrahim et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                α-mangostin,apoptosis,mitochondria,protein array,caspace 3/7,nf-κb

                Comments

                Comment on this article