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TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway

Item Type:Article
Title:TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway
Creators Name:Wendt, J. and von Haefen, C. and Hemmati, P. and Belka, C. and Doerken, B. and Daniel, P.T.
Abstract:The death ligand TRAIL has been suggested as a suitable biological agent for the selective induction of cell death in cancer cells. Moreover, TRAIL synergizes with DNA-damaging therapies such as chemotherapeutic drugs or ionizing irradiation (IR). Here, we show that synergy of TRAIL and IR, that is, crosssensitization between TRAIL and IR for induction of apoptosis, entirely depends on Bax proficiency in human DU145 and HCT116 carcinoma cells. DU145 prostate carcinoma cells that have lost Bax protein expression due to mutation fail to activate caspase-3 and -9 when exposed to TRAIL and IR. In contrast, TRAIL sensitized for IR-induced apoptosis and vice versa upon reconstitution of Bax expression. Notably, both DU145 and HCT116 still express significant levels of the multidomain proapoptotic Bcl-2 homolog Bak. This indicates that Bak is not sufficient to mediate cross-sensitization and synergism between IR and TRAIL. These data clearly establish distinct roles for Bax and Bak in linking the TRAIL death receptor pathway to the mitochondrial apoptosis signaling cascade upon DNA damage by IR.
Keywords:Apoptosis, Bax, Ionizing Irradiation, Mitochondrial Pathway, Synergy, TRAIL
Source:Oncogene
ISSN:0950-9232
Publisher:Nature Publishing Group (U.K.)
Volume:24
Number:25
Page Range:4052-4064
Date:1 January 2005
Official Publication:https://doi.org/10.1038/sj.onc.1208580
PubMed:View item in PubMed

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