@misc{10481/86510,
year = {2010},
month = {11},
url = {https://hdl.handle.net/10481/86510},
abstract = {Epigenetic modifications commonly associated with tumor development, such as histone
deacetylation, may influence the resistance of some tumor cells to tumor necrosis factor
(TNF)-related apoptosis-inducing ligand (TRAIL) by regulating gene transcription of components
of the TRAIL signalling pathway. In the present study we have analyzed the effect
of six different histone deacetylase inhibitors (HDACi), belonging to the four classic structural
families, on TRAIL-induced apoptosis in leukemic T cell lines. Non-toxic and functional
doses of all HDACi but apicidin, similarly sensitized different leukemic T cell lines
to TRAIL-induced apoptosis, while they showed no effect on the resistance of normal T
lymphocytes. Sensitizing doses of vorinostat, valproic acid, sodium butyrate and MS-275
regulated the expression of TRAIL-R2, c-FLIP and Apaf-1 in leukemic cells while TSA modulated
only the expression of Apaf-1. The synergistic effect of all HDACi and TRAIL was
inhibited in Bcl-2-overexpressing leukemic T cells. Thus, different HDACi may affect the
expression of different TRAIL-related genes, but regulation of the mitochondrial pathway
seems to be essential for the TRAIL sensitizing effect of HDACi in leukemic T cells. Overall,
HDACi represent a promising and safe strategy in combination with TRAIL for treatment of
T-cell leukaemia.},
organization = {This work was supported by the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (Grant PI060712 to C.R.-R.). J.C.M. was supported by a fellowship from the Ministerio de Educación y Ciencia.},
publisher = {ELSEVIER SCIENCE LTD},
keywords = {TRAIL},
keywords = {HDACi},
keywords = {Leukaemia},
keywords = {Apoptosis},
keywords = {Lymphocytes},
title = {HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosis},
doi = {10.1016/j.canlet.2010.04.029},
author = {Ruiz Magaña, María José and Carranza, Diana and Ortiz-Ferrón, Gustavo and Ruiz Ruiz, Carmen},
}