Universidad de Burgos RIUBU Principal Default Universidad de Burgos RIUBU Principal Default
  • español
  • English
  • français
  • Deutsch
  • português (Brasil)
  • italiano
Universidad de Burgos RIUBU Principal Default
  • Ayuda
  • Contact Us
  • Send Feedback
  • Acceso abierto
    • Archivar en RIUBU
    • Acuerdos editoriales para la publicación en acceso abierto
    • Controla tus derechos, facilita el acceso abierto
    • Sobre el acceso abierto y la UBU
    • español
    • English
    • français
    • Deutsch
    • português (Brasil)
    • italiano
    • español
    • English
    • français
    • Deutsch
    • português (Brasil)
    • italiano
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of RIUBUCommunities and CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    View Usage Statistics
    View Item 
    •   RIUBU Home
    • E-Prints
    • Grupos de investigación
    • Untitled
    • Artículos BIOORG
    • View Item
    •   RIUBU Home
    • E-Prints
    • Grupos de investigación
    • Untitled
    • Artículos BIOORG
    • View Item

    Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10259/4353

    Título
    Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal dysfunction leading to autophagy blockade and necrotic cell death in lung cancer
    Autor
    Rodilla, Ananda M. .
    Korrodi Gregório, Luís .
    Hernando Santa Cruz, ElsaUBU authority
    Manuel Manresa, Pilar .
    Quesada Pato, RobertoUBU authority
    Pérez Tomás, Ricardo .
    Soto Cerrato, Vanessa .
    Publicado en
    Biochemical Pharmacology. 2017. V. 126, p. 23–33
    Editorial
    Elsevier
    Fecha de publicación
    2017-02
    Abstract
    Current pharmacological treatments for lung cancer show very poor clinical outcomes, therefore, the development of novel anticancer agents with innovative mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient compared to normal cells, which favours cancer progression by promoting proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the use of ionophores to modulate intracellular pH appears as a promising new therapeutic strategy. Indeed, there is a growing body of evidence supporting ionophores as novel antitumour drugs. Despite this, little is known about the implications of pH deregulation and homeostasis imbalance triggered by ionophores at the cellular level. In this work, we deeply analyse for the first time the anticancer effects of tambjamine analogues, a group of highly effective anion selective ionophores, at the cellular and molecular levels. First, their effects on cell viability were determined in several lung cancer cell lines and patient-derived cancer stem cells, demonstrating their potent cytotoxic effects. Then, we have characterized the induced lysosomal deacidification, as well as, the massive cytoplasmic vacuolization observed after treatment with these compounds, which is consistent with mitochondrial swelling. Finally, the activation of several proteins involved in stress response, autophagy and apoptosis was also detected, although they were not significantly responsible for the cell death induced. Altogether, these evidences suggest that tambjamine analogues provoke an imbalance in cellular ion homeostasis that triggers mitochondrial dysfunction and lysosomal deacidification leading to a potent cytotoxic effect through necrosis in lung cancer cell lines and cancer stem cells.
    Palabras clave
    Anionophores
    Synthetictambjamine analogues
    Lysosomal dysfunction
    Autophagy blockade
    Necrosis
    URI
    http://hdl.handle.net/10259/4353
    Versión del editor
    http://dx.doi.org/10.1016/j.bcp.2016.11.022
    Collections
    • Artículos BIOORG
    Files in this item
    Nombre:
    Rodilla-BP_2017.pdf
    Tamaño:
    1.033Mb
    Formato:
    Adobe PDF
    Thumbnail
    FilesOpen

    Compartir

    Export

    RISMendeleyRefworksZotero
    • edm
    • marc
    • xoai
    • qdc
    • ore
    • ese
    • dim
    • uketd_dc
    • oai_dc
    • etdms
    • oai_openaire
    • rdf
    • mods
    • mets
    • didl
    • premis

    Citas

    Academic Search
    Show full item record