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Alpha-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-kappaB activation.

Dalen H, Neuzil J - Br. J. Cancer (2003)

Bottom Line: This lag was abolished by pretreatment of the cells with subapoptotic doses of alpha-tocopheryl succinate (alpha-TOS) or the proteasome inhibitor MG132.We conclude that alpha-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-kappaB 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Gade Institute, University of Bergen, Norway.

ABSTRACT
Activation of nuclear factor-kappaB (NF-kappaB) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL; Apo2L). Therefore, agents that suppress NF-kappaB 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 alpha-tocopheryl succinate (alpha-TOS) or the proteasome inhibitor MG132. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-kappaB, a process that was suppressed by cell pretreatment with alpha-TOS or MG132. Activation of NF-kappaB by TNF-alpha prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that alpha-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-kappaB 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.

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Related in: MedlinePlus

α-TOS sensitises Jurkat cells to TRAIL killing. Jurkat cells (0.5×106 ml−1) were pretreated with α-TOH, α-TOS, MG132 or hydrogen peroxide at the concentrations indicated (μM) for 4 h, or to TNF-α at 100 U ml−1 for 1 h, after which they were exposed to rhTRAIL at 40 ng ml−1. At time points indicated (A) or at 6 h (B) following TRAIL addition, cells were evaluated for apoptosis.
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fig3: α-TOS sensitises Jurkat cells to TRAIL killing. Jurkat cells (0.5×106 ml−1) were pretreated with α-TOH, α-TOS, MG132 or hydrogen peroxide at the concentrations indicated (μM) for 4 h, or to TNF-α at 100 U ml−1 for 1 h, after which they were exposed to rhTRAIL at 40 ng ml−1. At time points indicated (A) or at 6 h (B) following TRAIL addition, cells were evaluated for apoptosis.

Mentions: We next investigated whether preincubation with α-TOS might sensitise Jurkat cells to TRAIL. As shown in Figure 3Figure 3


Alpha-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-kappaB activation.

Dalen H, Neuzil J - Br. J. Cancer (2003)

α-TOS sensitises Jurkat cells to TRAIL killing. Jurkat cells (0.5×106 ml−1) were pretreated with α-TOH, α-TOS, MG132 or hydrogen peroxide at the concentrations indicated (μM) for 4 h, or to TNF-α at 100 U ml−1 for 1 h, after which they were exposed to rhTRAIL at 40 ng ml−1. At time points indicated (A) or at 6 h (B) following TRAIL addition, cells were evaluated for apoptosis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376774&req=5

fig3: α-TOS sensitises Jurkat cells to TRAIL killing. Jurkat cells (0.5×106 ml−1) were pretreated with α-TOH, α-TOS, MG132 or hydrogen peroxide at the concentrations indicated (μM) for 4 h, or to TNF-α at 100 U ml−1 for 1 h, after which they were exposed to rhTRAIL at 40 ng ml−1. At time points indicated (A) or at 6 h (B) following TRAIL addition, cells were evaluated for apoptosis.
Mentions: We next investigated whether preincubation with α-TOS might sensitise Jurkat cells to TRAIL. As shown in Figure 3Figure 3

Bottom Line: This lag was abolished by pretreatment of the cells with subapoptotic doses of alpha-tocopheryl succinate (alpha-TOS) or the proteasome inhibitor MG132.We conclude that alpha-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-kappaB 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Gade Institute, University of Bergen, Norway.

ABSTRACT
Activation of nuclear factor-kappaB (NF-kappaB) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL; Apo2L). Therefore, agents that suppress NF-kappaB 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 alpha-tocopheryl succinate (alpha-TOS) or the proteasome inhibitor MG132. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-kappaB, a process that was suppressed by cell pretreatment with alpha-TOS or MG132. Activation of NF-kappaB by TNF-alpha prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that alpha-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-kappaB 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.

Show MeSH
Related in: MedlinePlus