, Volume 14, Issue 5, pp 641–654 | Cite as

Cell cycle arrest in early mitosis and induction of caspase-dependent apoptosis in U937 cells by diallyltetrasulfide (Al2S4)

  • Claudia Cerella
  • Christiane Scherer
  • Silvia Cristofanon
  • Estelle Henry
  • Awais Anwar
  • Corinna Busch
  • Mathias Montenarh
  • Mario Dicato
  • Claus Jacob
  • Marc DiederichEmail author
Original Paper


Naturally occurring organic sulfur compounds (OSCs), such as linear allylsulfides from Allium species, are attracting attention in cancer research, since several OSCs were shown to act beneficially both in chemoprevention and in chemotherapy, while hardly exerting any harmful side effects. Hence, we investigated the possible role of different OSCs in the treatment of leukemia. Thereby, we found that the compounds tested in this study induced apoptosis in U937 cells, with an efficiency depending on the number of sulfides, and selected the most promising candidate, diallyltetrasulfide (Al2S4), for detailed mechanistic studies. Here we show that Al2S4 induced an accumulation of cells in early mitosis (G2/M phase), followed by the activation of caspase-dependent apoptosis. The compound counteracted different anti-apoptotic Bcl-2 family members (Bcl-xL, phospho-Bad and Bcl-2), promoted activation of Bax and Bak and induced the release of cytochrome c into the cytoplasm. Treatment by Al2S4 let to the identification of early apoptotic events including Bcl-xL degradation, Bak activation and release of cytochrome c followed by late events including Bcl-2 proteolysis, Bax activation, Bad dephosphorylation, caspase activation, nuclear fragmentation and phosphatidylserine exposure.


Diallyltetrasulfide Apoptosis Cell cycle Mitosis Leukemia Bax/Bak activation 



CC is a recipient of a postdoctoral Télévie-Luxembourg grant. CS and SC are recipients of a postdoctoral grant from the “Ministère de la Culture, de l’Enseignement supérieur et de la Recherche of Luxembourg”. Additionally the authors are indebted to several institutions for their support: Télévie Luxembourg, the ‘‘Fondation de Recherche Cancer et Sang’’ and ‘‘Recherches Scientifiques Luxembourg association”. Besides the authors thank “Een Häerz fir Kriibskrank Kanner” association, the Action Lions “Vaincre le Cancer”, the Foundation for Scientific Cooperation between Germany and Luxembourg, the Saarland University and the “Ministry of Economics and Science of Saarland” for additional support. Moreover, AA thanks the Saarland University for financial support.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Claudia Cerella
    • 1
  • Christiane Scherer
    • 1
    • 2
  • Silvia Cristofanon
    • 1
  • Estelle Henry
    • 1
  • Awais Anwar
    • 2
  • Corinna Busch
    • 3
  • Mathias Montenarh
    • 3
  • Mario Dicato
    • 1
  • Claus Jacob
    • 2
  • Marc Diederich
    • 1
    Email author
  1. 1.Laboratoire de Biologie Moléculaire et Cellulaire de CancerHôpital KirchbergLuxembourgLuxembourg
  2. 2.Division of Bioorganic Chemistry, School of PharmacySaarland UniversitySaarbruckenGermany
  3. 3.Division of Medicinal Biochemistry and Molecular BiologySaarland UniversityHomburgGermany

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