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Ehrhardt, H. ; Wachter, F. ; Grunert, M. ; Jeremias, I.

Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis.

Cell Death Dis. 4:e661 (2013)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Resting tumor cells represent a huge challenge during anticancer therapy due to their increased treatment resistance. TNF-related apoptosis-inducing ligand (TRAIL) is a putative future anticancer drug, currently in phases I and II clinical studies. We recently showed that TRAIL is able to target leukemia stem cell surrogates. Here, we tested the ability of TRAIL to target cell cycle-arrested tumor cells. Cell cycle arrest was induced in tumor cell lines and xenografted tumor cells in G0, G1 or G2 using cytotoxic drugs, phase-specific inhibitors or RNA interference against cyclinB and E. Biochemical or molecular arrest at any point of the cell cycle increased TRAIL-induced apoptosis. Accordingly, when cell cycle arrest was disabled by addition of caffeine, the antitumor activity of TRAIL was reduced. Most important for clinical translation, tumor cells from three children with B precursor or T cell acute lymphoblastic leukemia showed increased TRAIL-induced apoptosis upon knockdown of either cyclinB or cyclinE, arresting the cell cycle in G2 or G1, respectively. Taken together and in contrast to most conventional cytotoxic drugs, TRAIL exerts enhanced antitumor activity against cell cycle-arrested tumor cells. Therefore, TRAIL might represent an interesting drug to treat static-tumor disease, for example, during minimal residual disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cell Cycle Arrest; TRAIL; Apoptosis; DR5; Cyclins; Dna-binding Cooperativity ; Minimal Residual Disease ; Anticancer Therapies ; Leukemia Cells ; Cancer-therapy ; Death ; Xenografts ; Caspase-8 ; Insights ; Gene
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Zeitschrift Cell Death & Disease
Quellenangaben Band: 4, Heft: 6, Seiten: , Artikelnummer: e661 Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)