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Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection
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Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection

Published on: December 4, 2010

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TRAIL responses are enhanced by nuclear export inhibition in osteosarcoma

K L Phillips1, N Wright1, E McDermott1

  • 1Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1AF, UK.

Biochemical and Biophysical Research Communications
|August 1, 2019
PubMed

Insights

Leptomycin B enhances the anti-cancer effects of TRAIL therapy in osteosarcoma. This nuclear export inhibitor overcomes TRAIL resistance and sensitizes resistant cells, offering a potential new strategy for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) shows anti-cancer potential by inducing apoptosis.
  • TRAIL resistance and TRAIL-insensitive disease limit the efficacy of TRAIL-based therapies.
  • TRAIL-sensitizers are needed to enhance TRAIL activity and overcome resistance.

Purpose of the Study:

  • To investigate the potential of Leptomycin B as a TRAIL-sensitizer in osteosarcoma.
  • To evaluate the synergistic effects of Leptomycin B with TRAIL and death receptor agonists.
  • To determine if Leptomycin B overcomes TRAIL resistance in osteosarcoma cell lines.

Main Methods:

  • In vitro studies using osteosarcoma cell lines.
  • Treatment with Leptomycin B, TRAIL, and death receptor 5 agonistic antibodies.
  • Assessment of apoptosis induction and TRAIL sensitivity/resistance.
  • Evaluation of aldehyde dehydrogenase (ALDH) positive cell response.

Main Results:

  • Leptomycin B acts as a potent in vitro TRAIL-sensitizer in osteosarcoma cells.
  • Leptomycin B synergizes with TRAIL and death receptor 5 agonistic antibodies to induce apoptosis.
  • Leptomycin B sensitizes TRAIL-insensitive osteosarcoma cells to apoptosis.
  • ALDH-positive cells are not resistant to Leptomycin B and TRAIL-induced apoptosis.

Conclusions:

  • Leptomycin B is a promising TRAIL-sensitizer for osteosarcoma treatment.
  • Combining nuclear export inhibition with death receptor agonists is a potential therapeutic strategy.
  • Further research into selective nuclear export inhibitors is warranted for osteosarcoma therapy.
Keywords:
Aldehyde dehydrogenaseApoptosisDeath receptorLeptomycin BNuclear export inhibitorOsteosarcomaTRAIL

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