Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

Journal Article · Thu Sep 10 00:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.06.011· OSTI ID:22209794

Geel, Tessa M. ^[1]; Meiss, Gregor ^[2]; Gun, Bernardina T. van der; Kroesen, Bart Jan; Leij, Lou F. de ^[1]; Zaremba, Mindaugas; Silanskas, Arunas ^[3]; Kokkinidis, Michael ^[4]; Pingoud, Alfred ^[2]; Ruiters, Marcel H. ^[1]; Synvolux therapeutics, Groningen ^[5]; McLaughlin, Pamela M. ^[1]

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1. Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands)
2. Institute of Biochemistry, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)
3. Institute of Biotechnology, Vilnius LT-02241 (Lithuania)
4. IMBB/FORTH and University of Crete/Department of Biology, GR-71409 Heraklion/Crete (Greece)
5. Netherlands

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{sup Registered-Sign }: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.

• OSTI ID: 22209794
• Journal Information: Experimental Cell Research, Vol. 315, Issue 15; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CARCINOMAS
CLEAVAGE
DEUTERIUM IONS
DNA
ENDONUCLEASES
IN VIVO
LIPIDS
MICROSCOPY
MITOCHONDRIA
TUMOR CELLS