gms | German Medical Science

16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Deutsche Gesellschaft für Thoraxchirurgie

04.10. - 06.10.2007, Konstanz

Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5

Meeting Abstract

  • S. Frese - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland
  • M. Frese-Schaper - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland
  • A. C. Andres - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland
  • D. Miescher - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland
  • B. Zumkehr - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland
  • R. A. Schmid - Division of General Thoracic Surgery, University Hospital Berne and The Tiefenau Laboratory, Department of Clinical Research, University of Berne, Switzerland

Deutsche Gesellschaft für Thoraxchirurgie. 16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie. Konstanz, 04.-06.10.2007. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc07dgtF7

DOI: 10.3205/07dgt29, URN: urn:nbn:de:0183-07dgt293

Veröffentlicht: 22. März 2010

© 2010 Frese et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Tumor necrosis factor (TNF)-related apoptosisincluding ligand (Apo2L/TRAIL) belongs to the TNF family known to transduce their death signals via cell membrane receptors. Because it has been shown that Apo2L/TRAIL induces apoptosis

in tumor cells without or little toxicity to normal cells, this cytokine became of special interest for cancer research. Unfortunately, cancer cells are often resistant to Apo2L/TRAIL-induced apoptosis; however, this can be at least partially negotiated by parallel treatment with other substances, such as chemotherapeutic agents.

Here, we report that cardiac glycosides, which have been used for the treatment of cardiac failure for many years, sensitize lung cancer cells but not normal human peripheral blood mononuclear cells to Apo2L/TRAIL-induced apoptosis. Sensitization to Apo2L/TRAIL mediated by cardiac glycosides was accompanied by upregulation of death receptors 4 (DR4) and 5 (DR5) on both RNA and protein levels. The use of small interfering RNA revealed that up-regulation of death receptors in essential for the demonstrated augmentation of apoptosis. Blocking of up-regulation of DR4 and DR5 alone significantly reduced cell death after combined treatment with cardiac glycosides and Apo2L/TRAIL. Combined silencing of DR4 and DR 5 abrogated the ability of cardiac glycosides and Apo2L/TRAIL to induce apoptosis in an additive manner.

To our knowledge, this in the first demonstration that glycosides upregulate DR4 and DR5, thereby reverting the resistance of lung cancer cells to Apo5L/TRAIL-induced apoptosis. Our data suggest that the combination of Apo2/TRAIL and cardiac glycosides may be a new interesting anticancer treatment strategy.