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a-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-?B activation
Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology.
2003 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 88, no 1, 153-158 p.Article in journal (Refereed) Published
Abstract [en]

Activation of nuclear factor-?B (NF-?B) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L). Therefore, agents that suppress NF-?B activation may sensitise cells to TRAIL-dependent apoptosis. Exposure of Jurkat cells to TRAIL resulted in massive and saturable apoptosis induction, following an initial lag time. This lag was abolished by pretreatment of the cells with subapoptotic doses of a-tocopheryl succinate (a-TOS) or the proteasome inhibitor MGI32. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-?B, a process that was suppressed by cell pretreatment with a-TOS or MGI32. Activation of NF-?B by TNF-a prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that a-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-?B activation. This further supports the possibility that this semisynthetic analogue of vitamin E is a potential adjuvant in cancer treatment, such as in the case of TRAIL-mediated inhibition of cancer.

Place, publisher, year, edition, pages
2003. Vol. 88, no 1, 153-158 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27722DOI: 10.1038/sj.bjc.6600683Local ID: 12460OAI: oai:DiVA.org:liu-27722DiVA: diva2:248274
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13

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Neuzil, Jiri

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