Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies

Ruggero De Maria Marchiano, Concetta Conticello, Daniela Martinetti, Luana Adamo, Simona Buccheri, Raffaella Giuffrida, Nunziatina Parrinello, Laura Lombardo, Gabriele Anastasi, Gabriella Amato, Maide Cavalli, Annalisa Chiarenza, Rosario Giustolisi, Massimo Gulisano, Francesco Di Raimondo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

55 Citazioni (Scopus)

Abstract

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor currently used for the treatment of alcoholism. Here, we show that multiple myeloma (MM) cell lines and primary cells from newly diagnosed and relapsed/resistant patients affected by MM, acute myeloid and lymphoblastic leukemia are significantly sensitive to DSF alone and in combination with copper. These effects are present at doses lower than those achievable in vivo after DSF standard administration. The cytotoxic effect achieved by this treatment is comparable to that obtained by conventional chemotherapy and is absent in normal hematopoietic cells. In addition, we found that DSF plus copper induces loss of mitochondrial membrane potential, triggers reactive oxygen species (ROS) production and activates executioner caspases. DSF-copper-induced apoptosis and caspases activation are strongly reversed by antioxidant N-acetylcysteine, thus indicating a critical role of ROS. These results might suggest the use of the old drug DSF, alone or in combination with copper, in the treatment of hematological malignancies. Copyright © 2012 UICC.
Lingua originaleEnglish
pagine (da-a)2197-2203
Numero di pagine7
RivistaInternational Journal of Cancer
Volume131
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Acetylcysteine
  • Antineoplastic Agents
  • Apoptosis
  • Cancer Research
  • Caspases
  • Cell Line, Tumor
  • Copper
  • Disulfiram
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Humans
  • Leukemia, Myeloid, Acute
  • Membrane Potentials
  • Mitochondrial Membranes
  • Multiple Myeloma
  • Oncology
  • Oxidative Stress
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Reactive Oxygen Species
  • acute leukemia
  • apoptosis
  • disulfiram
  • mitochondria
  • multiple myeloma

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