Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restri...

Full description

Saved in:
Bibliographic Details
Published in:Experimental cell research 2009-09, Vol.315 (15), p.2487-2495
Main Authors: Geel, Tessa M., Meiss, Gregor, van der Gun, Bernardina T., Kroesen, Bart Jan, de Leij, Lou F., Zaremba, Mindaugas, Šilanskas, Arūnas, Kokkinidis, Michael, Pingoud, Alfred, Ruiters, Marcel H., McLaughlin, Pamela M., Rots, Marianne G.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Amino Acid Chloromethyl Ketones - metabolism
APOPTOSIS
Apoptosis - physiology
CARCINOMAS
Caspase 3 - metabolism
Cell Line, Tumor
Cellular biology
CLEAVAGE
Clinical trials
DEUTERIUM IONS
DNA
DNA Fragmentation
ENDONUCLEASES
Endonucleases - metabolism
Enzyme Inhibitors - metabolism
Female
Fibroblasts - cytology
Fibroblasts - physiology
Histones - metabolism
Humans
IN VIVO
LIPIDS
MICROSCOPY
MITOCHONDRIA
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Phosphatidylethanolamines - metabolism
Protein delivery
Pyridinium Compounds - metabolism
Restriction endonucleases
Signal Transduction - physiology
TNF-Related Apoptosis-Inducing Ligand - genetics
TNF-Related Apoptosis-Inducing Ligand - metabolism
TRAIL resistance
TUMOR CELLS
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restriction endonucleases to directly digest DNA in vivo, thereby circumventing the caspase cascade. For this purpose, we delivered enzymatically active endonucleases via the cationic amphiphilic lipid SAINT-18 ®:DOPE to both TRAIL-sensitive and insensitive ovarian carcinoma cells (OVCAR and SKOV-3, respectively). Functional nuclear localization after delivery of various endonucleases (BfiI, PvuII and NucA) was indicated by confocal microscopy and genomic cleavage analysis. For PvuII, analysis of mitochondrial damage demonstrated extensive apoptosis both in SKOV-3 and OVCAR. This study clearly demonstrates that cellular delivery of restriction endonucleases holds promise to serve as a novel therapeutic tool for the treatment of resistant ovarian carcinomas.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2009.06.011