Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL
- 19 April 2001
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 20 (17) , 2190-2196
- https://doi.org/10.1038/sj.onc.1204318
Abstract
A combination of antitumor approaches acting on different death pathways seems ideal for increasing therapeutic responses, especially when defined resistance mechanisms interfere with individual cellular processes. Apoptosis pathways triggered by ionizing radiation (XRT) and the death ligand TRAIL were analysed in Jurkat lymphoma cells. Both induced the activation of caspase-8, caspase-3, BID and mitochondrial potential loss. TRAIL induced apoptosis required caspase-8, whereas it was not essential for radiation induced apoptosis. The inhibition of mitochondrial damage by Bcl-2 abrogated XRT induced apoptosis and caspase activation, but only marginally attenuated TRAIL induced cell death. The combined treatment with TRAIL and XRT exerted additive apoptotic effects in control cells, whereas highly synergistic effects occurred in cells overexpressing Bcl-2. In addition, a strong effect of TRAIL on radiation induced clonogenic cell death was found. In conclusion, TRAIL seems to be of high potential value for a combination with ionizing radiation in tumor therapy.Keywords
This publication has 25 references indexed in Scilit:
- Differential role of caspase-8 and BID activation during radiation- and CD95-induced apoptosisOncogene, 2000
- Safety and antitumor activity of recombinant soluble Apo2 ligandJournal of Clinical Investigation, 1999
- Apaf-1 and Caspase-9 in p53-Dependent Apoptosis and Tumor InhibitionScience, 1999
- Targeted Disruption of the Mouse Caspase 8 Gene Ablates Cell Death Induction by the TNF Receptors, Fas/Apo1, and DR3 and Is Lethal PrenatallyImmunity, 1998
- FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling ComplexCell, 1996
- FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosisCell, 1995
- Expression of the bcl‐2 gene family in normal and malignant breast tissue: Low bax‐α expression in tumor cells correlates with resistance towards apoptosisInternational Journal of Cancer, 1995
- Tumor suppressor p53 is a direct transcriptional activator of the human bax geneCell, 1995
- p53 is required for radiation-induced apoptosis in mouse thymocytesNature, 1993
- Comparative Human Cellular Radiosensitivity: III. γ-radiation Survival of Cultured Skin Fibroblasts and Resting T-lymphocytes from the Peripheral Blood of the Same IndividualInternational Journal of Radiation Biology, 1991