Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

Tessa M. Geel, Gregor Meiss, Bernardina T. van der Gun, Bart Jan Kroesen, Lou F. de Leij, Mindaugas Zaremba, Arunas Silanskas, Michael Kokkinidis, Alfred Pingoud, Marcel H. Ruiters, Pamela M. McLaughlin, Marianne G. Rots*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

7 Citaten (Scopus)

Samenvatting

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 (R):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. (C) 2009 Elsevier Inc. All rights reserved.

Originele taal-2English
Pagina's (van-tot)2487-2495
Aantal pagina's9
TijdschriftExperimental Cell Research
Volume315
Nummer van het tijdschrift15
DOI's
StatusPublished - 10-sep-2009

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