Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway

2004 ◽  
Vol 11 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Alessandra Insinga ◽  
Silvia Monestiroli ◽  
Simona Ronzoni ◽  
Vania Gelmetti ◽  
Francesco Marchesi ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Death Receptor ◽  
Death Receptor Pathway ◽  
Tumor Selective

scholarly journals Erratum: Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway

2005 ◽  
Vol 11 (2) ◽  
pp. 233-233 ◽  
Author(s):  
A Insinga ◽  
S Monestiroli ◽  
S Ronzoni ◽  
V Gelmetti ◽  
F Marchesi ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Death Receptor ◽  
Death Receptor Pathway ◽  
Tumor Selective

Lead induces apoptosis in mouse TM3 Leydig cells through the Fas/FasL death receptor pathway

2017 ◽  
Vol 56 ◽  
pp. 99-105 ◽  
Author(s):  
Xiuyuan He ◽  
Jing Wu ◽  
Liyun Yuan ◽  
Feng Lin ◽  
Jine Yi ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Death Receptor ◽  
Death Receptor Pathway

The Protective Role of Selenium Against AFB1-Induced Liver Apoptosis by Death Receptor Pathway in Broilers

2019 ◽  
Vol 191 (2) ◽  
pp. 453-463 ◽  
Author(s):  
Bangyuan Wu ◽  
Muhammad Jameel Mughal ◽  
Jing Fang ◽  
Xi Peng
Keyword(s):  
Death Receptor ◽  
Protective Role ◽  
Death Receptor Pathway

Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells

2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Death Receptor ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Death Receptor Pathway ◽  
L02 Cells

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.

scholarly journals Differential activation of the death receptor pathway in human target cells induced by cytotoxic T lymphocytes showing different kinetics of killing

Haematologica ◽  
2007 ◽  
Vol 92 (12) ◽  
pp. 1671-1678 ◽  
Author(s):  
J. F. de Vries ◽  
P. A. von dem Borne ◽  
S. A.P. van Luxemburg-Heijs ◽  
M. H.M. Heemskerk ◽  
R. Willemze ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Death Receptor ◽  
Target Cells ◽  
Differential Activation ◽  
Death Receptor Pathway ◽  
Kinetics Of

scholarly journals Molecular Determinants of the Caspase-promoting Activity of Smac/DIABLO and Its Role in the Death Receptor Pathway

2000 ◽  
Vol 275 (46) ◽  
pp. 36152-36157 ◽  
Author(s):  
Srinivasa M. Srinivasula ◽  
Pinaki Datta ◽  
Xue-Jun Fan ◽  
Teresa Fernandes-Alnemri ◽  
Ziwei Huang ◽  
...  
Keyword(s):  
Death Receptor ◽  
Death Receptor Pathway ◽  
Molecular Determinants

scholarly journals Inhibition of the Death Receptor Pathway by cFLIP Confers Partial Engraftment of MHC Class I-Deficient Stem Cells and Reduces Tumor Clearance in Perforin-Deficient Mice

2001 ◽  
Vol 167 (8) ◽  
pp. 4230-4237 ◽  
Author(s):  
Mesha Austin Taylor ◽  
Preet M. Chaudhary ◽  
Jennifer Klem ◽  
Vinay Kumar ◽  
John D. Schatzle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mhc Class I ◽  
Death Receptor ◽  
Class I ◽  
Death Receptor Pathway ◽  
Tumor Clearance ◽  
Deficient Mice

Rexinoid-Triggered Differentiation and Tumor-Selective Apoptosis of AML by Protein Kinase A-Mediated De-Subordination.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2235-2235
Author(s):  
Ettore Mariano Schiavone ◽  
Lucia Altucci ◽  
Mariacarla De Simone ◽  
Felicetto Ferrara ◽  
Aurélie Rossin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
Hdac Inhibitors ◽  
Death Receptor ◽  
Phosphodiesterase Inhibitors ◽  
Camp Phosphodiesterase ◽  
Tumor Selective ◽  
Kinase A

Abstract Apart from PML-RARα acute promyelocytic leukemia all other acute myeloid leukemias (AML) are unresponsive to retinoid differentiation therapy. However, in our study we show that elevating the levels of cyclic AMP (cAMP) confers onto retinoid X receptor (RXR)-selective agonists (“rexinoids”) the ability to induce terminal granulocyte differentiation and apoptosis of all-trans retinoic acid-resistant and insensitive AML cell lines and patients’ AML blasts. Protein kinase A activation leads to co-repressor release from the RAR subunit of the RAR-RXR heterodimer, resulting in “de-subordination” of otherwise silent RXR, which acquires transcriptional competence in response to cognate ligands. Rexinoid-cAMP induction of endogenous RARβ is blunted in mouse embryo fibroblasts lacking RARs, but re-introduction of exogenous RARα re-establishes responsiveness, thus confirming that the RARα-RXR heterodimer is the rexinoid mediator. The apoptogenic effect of this treatment involves enhanced expression of the death receptor DR5 and its cognate ligand, the tumor necrosis factor-related apoptosis inducing ligand (TRAIL), both of which are known to induce apoptosis in a tumor cell-selective manner and lead to the activation of initiator caspases. Immunohistochemistry confirmed induction of TRAIL and DR5 in AML patient blasts cultured “ex vivo”. AML patients’ blasts responded to rexinoid-cAMP combination treatment with induction of maturation and apoptosis, independent of karyotype, immunophenotype, and FAB classification. Clonogenic assays revealed complete inhibition of blast clonogenicity in four out of five tested samples. Indeed, it is known that cAMP levels can be elevated also by treating cells with 3′, 5′-cAMP phosphodiesterase inhibitors (PDEi’s). These observation and the clinical availability of the corresponding drugs provide a rationale for initiating clinical studies addressing the efficacy of combinatorial PDEi-rexinoid therapy in AML patients. Together with our recent finding that a very promising class of epigenetic anti-tumor drugs operates through activation of TRAIL expression (Nat Med2005, 11(1):7784), the possibility to target both the ligand (TRAIL) by HDAC inhibitors and the cognate receptors (DR4, DR5) by the above described rexinoid crosstalk may represent a promising therapeutic option which might lead, despite the genetic, morphologic, and clinical variability of AML, to a novel therapeutic option for AML patients by inducing a tumor-selective death pathway.

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