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

Autor:	Melendez ME; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Silva-Oliveira RJ; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Silva Almeida Vicente AL; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Rebolho Batista Arantes LM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Carolina de Carvalho A; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Epstein AL; UMR1179, INSERM-UVSQ, Handicap Neuromusculaire, Biotherapie et Pharmacologie Appliquées, Université de Versailles-Saint Quentin en Yvelines, Versailles, France., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.; Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal., Carvalho AL; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Jun 05; Vol. 9 (43), pp. 27233-27241. Date of Electronic Publication: 2018 Jun 05 (Print Publication: 2018).
DOI:	10.18632/oncotarget.25519
Abstrakt:	Apoptosis induction has emerged as a treatment option for anticancer therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein, is a potent and specific pro-apoptotic protein ligand, which activates the extrinsic apoptosis pathway of the cell death receptors. Here we describe the construction and characterization of a new soluble TRAIL, sfTRAIL, stabilized with the trimerization Foldon domain from the Fibritin protein of the bacteriophage T4. Supernatants of 0.22 μM-filtered supernatants were produced in Vero-transduced cells with HSV1-derived viral amplicon vectors. Experiments were undertaken in two known TRAIL-sensitive (U373 and MDA.MB.231) and two TRAIL-resistant (MCF7 and A549) cell lines, to determine (i) whether the sfTRAIL protein is synthetized and, (ii) whether sfTRAIL could induce receptor-mediated apoptosis. Our results showed that sfTRAIL was able to induce apoptosis at concentrations as low as 1899.29 pg/mL (27.71 pM), independently of caspase-9 activation, and reduction in cell viability at 998.73 fM. Competing Interests: CONFLICTS OF INTEREST Authors MEM and ALC have a patent for this technology.
Databáze:	MEDLINE
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