93
views
0
recommends
+1 Recommend
0 collections
    13
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Molecular biology of cantharidin in cancer cells

      review-article

      Read this article at

      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

          Herbal medicine is one of the forms of traditional medical practice. Traditional Chinese medicine (TCM) and traditional Vietnamese medicine (TVM) are well-known for their long-standing tradition of herbal medicine.

          Secreted by many species of blister beetle, most notably by the 'Spanish fly' ( Lytta vesicatoria), cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). Blister beetle has been used in Asian traditional medicine to treat Molluscum contagiosum virus (MCV) infections and associated warts, and is now also used for cancer treatment. A combination of both genomic and postgenomic techniques was used in our studies to identify candidate genes affecting sensitivity or resistance to cantharidin. Cantharidin was not found to be related to multidrug resistance phenotype, suggesting its potential usefulness for the treatment of refractory tumors. Oxidative stress response genes diminish the activity of cantharidin by inducing DNA strand breaks which may be subject to base excision repair and induce apoptosis in a p53- and Bcl2-dependent manner.

          Cantharidin is one of many natural products used in traditional Chinese medicine and traditional Vietnamese medicine for cancer treatment. Combined methods of pharmaceutical biology and molecular biology can help elucidate modes of action of these natural products.

          Related collections

          Most cited references90

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

          DNA damage-induced apoptosis.

          Unicellular organisms respond to the presence of DNA lesions by activating cell cycle checkpoint and repair mechanisms, while multicellular animals have acquired the further option of eliminating damaged cells by triggering apoptosis. Defects in DNA damage-induced apoptosis contribute to tumorigenesis and to the resistance of cancer cells to a variety of therapeutic agents. The intranuclear mechanisms that signal apoptosis after DNA damage overlap with those that initiate cell cycle arrest and DNA repair, and the early events in these pathways are highly conserved. In addition, multiple independent routes have recently been traced by which nuclear DNA damage can be signalled to the mitochondria, tipping the balance in favour of cell death rather than repair and survival. Here, we review current knowledge of nuclear DNA damage signalling, giving particular attention to interactions between these nuclear events and apoptotic processes in other intracellular compartments.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            ASPP proteins specifically stimulate the apoptotic function of p53.

            We identified a family of proteins termed ASPP. ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. Inhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo. Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction. The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mechanisms of human DNA repair: an update.

              The human genome, comprising three billion base pairs coding for 30000-40000 genes, is constantly attacked by endogenous reactive metabolites, therapeutic drugs and a plethora of environmental mutagens that impact its integrity. Thus it is obvious that the stability of the genome must be under continuous surveillance. This is accomplished by DNA repair mechanisms, which have evolved to remove or to tolerate pre-cytotoxic, pre-mutagenic and pre-clastogenic DNA lesions in an error-free, or in some cases, error-prone way. Defects in DNA repair give rise to hypersensitivity to DNA-damaging agents, accumulation of mutations in the genome and finally to the development of cancer and various metabolic disorders. The importance of DNA repair is illustrated by DNA repair deficiency and genomic instability syndromes, which are characterised by increased cancer incidence and multiple metabolic alterations. Up to 130 genes have been identified in humans that are associated with DNA repair. This review is aimed at updating our current knowledge of the various repair pathways by providing an overview of DNA-repair genes and the corresponding proteins, participating either directly in DNA repair, or in checkpoint control and signaling of DNA damage.
                Bookmark

                Author and article information

                Journal
                Chin Med
                Chinese Medicine
                BioMed Central (London )
                1749-8546
                2007
                4 July 2007
                : 2
                : 8
                Affiliations
                [1 ]State of Maryland Department of Health and Mental Hygiene, Maryland, USA
                [2 ]Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
                [3 ]Joanneum Research, Graz, Austria
                [4 ]Institute of Toxicology, University of Mainz, Mainz, Germany
                [5 ]Pharmaceutical Biology (C015), German Cancer Research Centre, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
                Article
                1749-8546-2-8
                10.1186/1749-8546-2-8
                1934358
                17610718
                84f6727a-fb3b-4d58-b7b9-981c70f5fab1
                Copyright © 2007 Rauh et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 February 2007
                : 4 July 2007
                Categories
                Review

                Complementary & Alternative medicine
                Complementary & Alternative medicine

                Comments

                Comment on this article