scholarly journals p53-Independent Endoplasmic Reticulum Stress-Mediated Cytotoxicity of a Newcastle Disease Virus Strain in Tumor Cell Lines

2007 ◽  
Vol 81 (6) ◽  
pp. 2817-2830 ◽  
Author(s):  
Zsolt Fábián ◽  
Christine M. Csatary ◽  
József Szeberényi ◽  
Laszlo K. Csatary
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Tumor Cell ◽  
Newcastle Disease Virus ◽  
Cell Lines ◽  
Newcastle Disease ◽  
Apoptotic Cell ◽  
Transformed Cells ◽  
Tumor Cell Lines

ABSTRACT While Newcastle disease virus (NDV) causes serious infections in birds, it is apparently nonpathogenic in mammalian species, including humans. Previous observations and small-scale clinical trials indicated that NDV exerts oncolytic effects. Isolates of NDV were found to have selective affinity to transformed cells. We previously showed that the attenuated NDV strain MTH-68/H causes apoptotic cell death in cultures of PC12 rat pheochromocytoma cells. The aim of the present study was to extend MTH-68/H cytotoxicity testing with human tumor cell lines and to analyze certain biochemical aspects of its oncolytic effect. MTH-68/H was found to be able to kill a wide range of transformed cells by apoptosis. While caspase-8 and caspase-9 are not involved in MTH-68/H-induced apoptosis, activation of caspase-3 and caspase-12 was detected in virus-infected PC12 cells. A human glioblastoma cell line with repressible expression of the p53 protein did not show any difference in MTH-68/H sensitivity in its p53-expressing and p53-depleted states, indicating that the apoptotic process induced by MTH-68/H does not depend on p53. Apoptosis was accompanied by virus replication in two tumor cell lines tested (PC12 cells and HeLa human cervical cells), and signs of endoplasmic reticulum stress (phosphorylation of protein kinase R-like endoplasmic reticulum kinase and eIF2α) were also detected in transformed cells. In contrast, proliferation of nontransformed mouse and rat fibroblast cell lines and human primary fibroblasts was not affected by MTH-68/H treatment. MTH-68/H thus selectively kills tumor cell cultures by inducing endoplasmic reticulum stress leading to p53-independent apoptotic cell death.

scholarly journals Adenovirus encoding HIV-1 Vpr activates caspase 9 and induces apoptotic cell death in both p53 positive and negative human tumor cell lines

Oncogene ◽  
2002 ◽  
Vol 21 (30) ◽  
pp. 4613-4625 ◽  
Author(s):  
Karuppiah Muthumani ◽  
Donghui Zhang ◽  
Daniel S Hwang ◽  
Sagar Kudchodkar ◽  
Nathanael S Dayes ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Caspase 9 ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Hiv 1

scholarly journals Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines

2006 ◽  
Vol 80 (11) ◽  
pp. 5145-5155 ◽  
Author(s):  
Sateesh Krishnamurthy ◽  
Toru Takimoto ◽  
Ruth Ann Scroggs ◽  
Allen Portner
Keyword(s):  
Signal Transduction ◽  
Tumor Cell ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Cell Lines ◽  
Newcastle Disease ◽  
Signal Transduction Pathway ◽  
Tumor Cell Lines ◽  
Transduction Pathway

ABSTRACT Newcastle disease virus (NDV) is a negative-strand RNA virus with oncolytic activity against human tumors. Its effectiveness against tumors and safety in normal tissue have been demonstrated in several clinical studies. Here we show that the spread of NDV infection is drastically different in normal cell lines than in tumor cell lines and that the two cell types respond differently to beta interferon (IFN-β) treatment. NDV rapidly replicated and killed HT-1080 human fibrosarcoma cells but spread poorly in CCD-1122Sk human skin fibroblast cells. Pretreatment with endogenous or exogenous IFN-β completely inhibited NDV replication in normal cells but had little or no effect in tumor cells. Thus, the outcome of NDV infection appeared to depend on the response of uninfected cells to IFN-β. To investigate their differences in IFN responsiveness, we analyzed and compared the expression and activation of components of the IFN signal transduction pathway in these two types of cells. The levels of phosphorylated STAT1 and STAT2 and that of the ISGF3 complex were markedly reduced in IFN-β-treated tumor cells. Moreover, cDNA microarray analysis revealed significantly fewer IFN-regulated genes in the HT-1080 cells than in the CDD-1122Sk cells. This finding suggests that tumor cells demonstrate a less-than-optimum antiviral response because of a lesion in their IFN signal transduction pathway. The rapid spread of NDV in HT-1080 cells appears to be caused by their deficient expression of anti-NDV proteins upon exposure to IFN-β.

Novel proteasome-inhibitory syrbactin analogs inducing endoplasmic reticulum stress and apoptosis in hematological tumor cell lines

2011 ◽  
Vol 82 (6) ◽  
pp. 600-609 ◽  
Author(s):  
Ashish Anshu ◽  
Simmy Thomas ◽  
Puneet Agarwal ◽  
Tannya R. Ibarra-Rivera ◽  
Michael C. Pirrung ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Hematological Tumor

Correlation between Potassium Channel Expression and Sensitivity to Drug-induced Cell Death in Tumor Cell Lines

2014 ◽  
Vol 20 (2) ◽  
pp. 189-200 ◽  
Author(s):  
Luigi Leanza ◽  
Paul O’Reilly ◽  
Anne Doyle ◽  
Elisa Venturini ◽  
Mario Zoratti ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Potassium Channel ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Drug Induced ◽  
Channel Expression

scholarly journals Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation

2011 ◽  
Vol 2 (3) ◽  
pp. 419-422 ◽  
Author(s):  
VESNA BUCAN ◽  
CLAUDIA Y.U. CHOI ◽  
ANDREA LAZARIDIS ◽  
PETER M. VOGT ◽  
KERSTIN REIMERS
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Lines ◽  
Solid Tumor ◽  
Transmembrane Protein ◽  
Tumor Cell Lines ◽  
Mcf 7

scholarly journals Cathepsin B activity in human lung tumor cell lines: ultrastructural localization, pH sensitivity, and inhibitor status at the cellular level.

1994 ◽  
Vol 42 (7) ◽  
pp. 917-929 ◽  
Author(s):  
E Spiess ◽  
A Brüning ◽  
S Gack ◽  
B Ulbricht ◽  
H Spring ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Tumor Cell ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Cathepsin B ◽  
Lung Tumor ◽  
Cell Types ◽  
Cellular Level ◽  
Tumor Cell Lines

We investigated the appearance and activity of the cysteine proteinase cathepsin B and its physiological inhibitors, stefins A and B, at the cellular level in human tumor cell lines HS-24, derived from a primary lung tumor (squamous cell), and SB-3, derived from a metastasis (lung adenocarcinoma). In addition to cathepsin B, these tumor cells also expressed the immunologically and functionally related cathepsin L, but not cathepsin H. Stefin A was found in HS-24 but not in SB-3 cells; stefin B was found in both cell types. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized and quantified. Thus, the cellular cathepsin B kinetics for the synthetic substrates Z-Arg-Arg-4M beta NA and Z-Val-Lys-Lys-Arg-4M beta NA, its pH dependence and inhibition by E64, stefins A and B, and cystatin C could be determined. From these measurements it appeared that the enzyme exhibited different cleavage rates for these substrates in the different cell types, showed considerable cleavage activity at neutral pH, which was stable under these conditions for extended time periods, and was highly sensitive to the inhibitors E64 and cystatin C but was considerably less sensitive to stefins, particularly stefin A. By conventional light microscopy, confocal laser scanning microscopy, and electron microscopy the enzymatic activity was localized in lysosomes, as expected, but also in the endoplasmic reticulum, nuclear membrane, and plasma membrane. The endoplasmic reticulum is a site at which only pre-mature enzyme forms exist, which are usually not active. The appearance of enzymatic activity at the plasma membrane confirms earlier biochemical and immunofluorescence microscopic investigations. The different sites of localization within the cells make it likely that different forms of the enzyme are expressed simultaneously, which follow alternate ways of processing and sorting. Taken together, the results support an involvement of the enzyme under extracellular conditions in degradative processes.

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