Related Experiment Videos
Alpha-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-kappaB
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.
Insights
Alpha-tocopheryl succinate (alpha-TOS) sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by inhibiting nuclear factor-kappaB (NF-kappaB) activation. This finding supports alpha-TOS as a potential adjuvant therapy for cancer treatment.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Nuclear factor-kappaB (NF-kappaB) activation can inhibit apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
- Agents suppressing NF-kappaB may enhance TRAIL-mediated apoptosis, suggesting potential therapeutic strategies in cancer treatment.
Purpose of the Study:
- To investigate whether alpha-tocopheryl succinate (alpha-TOS) can sensitize cells to TRAIL-induced apoptosis.
- To elucidate the role of NF-kappaB activation in TRAIL resistance and whether alpha-TOS affects this pathway.
Main Methods:
- Jurkat cells were exposed to TRAIL, with or without pretreatment with alpha-TOS or MG132 (a proteasome inhibitor).
- NF-kappaB activation was assessed following TRAIL exposure.
- The effect of TNF-alpha-induced NF-kappaB activation on TRAIL sensitivity was examined.
Main Results:
- TRAIL induced apoptosis in Jurkat cells after a lag phase, which was abolished by alpha-TOS or MG132 pretreatment.
- TRAIL exposure led to rapid, transient NF-kappaB activation, suppressed by alpha-TOS or MG132.
- Prior NF-kappaB activation by TNF-alpha increased resistance to TRAIL-mediated apoptosis.
Conclusions:
- Alpha-tocopheryl succinate (alpha-TOS) sensitizes cells to TRAIL-induced apoptosis, partly through the inhibition of NF-kappaB activation.
- This study supports the potential of alpha-TOS as an adjuvant in cancer therapy, particularly in conjunction with TRAIL-based treatments.