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Construction and characterization of a new TRAIL soluble form, active at picomolar concentrations

Matias Eliseo Melendez1, Renato José Silva-Oliveira1, Anna Luiza Silva Almeida Vicente1

  • 1Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.

Oncotarget
|June 23, 2018
PubMed

Insights

Researchers developed a novel soluble form of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), called sfTRAIL, which effectively induces cancer cell apoptosis. This new TRAIL variant shows potent cell death induction at very low concentrations.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Apoptosis induction is a key strategy in anticancer therapy.
  • Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a specific pro-apoptotic protein that triggers extrinsic cell death pathways.
  • Soluble TRAIL variants are being investigated to enhance therapeutic efficacy.

Purpose of the Study:

  • To construct and characterize a new stabilized soluble TRAIL protein, sfTRAIL.
  • To evaluate the synthesis and apoptotic potential of sfTRAIL in cancer cell lines.
  • To determine the effective concentration of sfTRAIL for inducing apoptosis and reducing cell viability.

Main Methods:

  • Construction of sfTRAIL using a trimerization Foldon domain from bacteriophage T4.
  • Production of sfTRAIL in Vero cells using HSV1-derived viral amplicon vectors.
  • Testing sfTRAIL efficacy in TRAIL-sensitive (U373, MDA.MB.231) and TRAIL-resistant (MCF7, A549) cell lines.

Main Results:

  • sfTRAIL was successfully synthesized and produced.
  • sfTRAIL induced apoptosis in cancer cells at concentrations as low as 27.71 pM.
  • A reduction in cell viability was observed at femtomolar concentrations (998.73 fM), independent of caspase-9 activation.

Conclusions:

  • The engineered sfTRAIL protein is a potent inducer of apoptosis.
  • sfTRAIL demonstrates significant potential as an anticancer therapeutic agent.
  • The study validates sfTRAIL's ability to trigger receptor-mediated apoptosis effectively.
Keywords:
TRAILamplicon vectorsapoptosiscancer treatment

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