Limits...
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.

Show MeSH

Related in: MedlinePlus

TRAIL is a potent inducer of apoptosis in Jurkat cells. Jurkat T lymphoma cells (0.5×106 ml−1) were exposed to the vehicle (A–C) or 40 ng ml−1 rhTRAIL (D–F), processed for TEM, observed, and images taken at the following magnifications: A, D–1800×; B–5000×; C, F–18 000×; and E–7000×; M-mitotic cell; I–cell in the interphase; Mi–mitochondrium; Nu–nucleolus; V–vacuole; *apoptotic cell; **nucleus with condensed chromatin.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2376774&req=5

fig1: TRAIL is a potent inducer of apoptosis in Jurkat cells. Jurkat T lymphoma cells (0.5×106 ml−1) were exposed to the vehicle (A–C) or 40 ng ml−1 rhTRAIL (D–F), processed for TEM, observed, and images taken at the following magnifications: A, D–1800×; B–5000×; C, F–18 000×; and E–7000×; M-mitotic cell; I–cell in the interphase; Mi–mitochondrium; Nu–nucleolus; V–vacuole; *apoptotic cell; **nucleus with condensed chromatin.

Mentions: The aim of the present study was to determine whether the semisynthetic vitamin E analogue, α-TOS, could enhance the sensitivity of Jurkat T lymphoma cells to the induction of apoptosis by the immunological agent TRAIL. For initiation of apoptosis, we used rhTRAIL that was expressed in bacterial cells. As shown in Figures 1Figure 1


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)

TRAIL is a potent inducer of apoptosis in Jurkat cells. Jurkat T lymphoma cells (0.5×106 ml−1) were exposed to the vehicle (A–C) or 40 ng ml−1 rhTRAIL (D–F), processed for TEM, observed, and images taken at the following magnifications: A, D–1800×; B–5000×; C, F–18 000×; and E–7000×; M-mitotic cell; I–cell in the interphase; Mi–mitochondrium; Nu–nucleolus; V–vacuole; *apoptotic cell; **nucleus with condensed chromatin.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: TRAIL is a potent inducer of apoptosis in Jurkat cells. Jurkat T lymphoma cells (0.5×106 ml−1) were exposed to the vehicle (A–C) or 40 ng ml−1 rhTRAIL (D–F), processed for TEM, observed, and images taken at the following magnifications: A, D–1800×; B–5000×; C, F–18 000×; and E–7000×; M-mitotic cell; I–cell in the interphase; Mi–mitochondrium; Nu–nucleolus; V–vacuole; *apoptotic cell; **nucleus with condensed chromatin.
Mentions: The aim of the present study was to determine whether the semisynthetic vitamin E analogue, α-TOS, could enhance the sensitivity of Jurkat T lymphoma cells to the induction of apoptosis by the immunological agent TRAIL. For initiation of apoptosis, we used rhTRAIL that was expressed in bacterial cells. As shown in Figures 1Figure 1

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