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Brevinin-2R semi-se...
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Ghavami, SaeidDepartment of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
(author)
Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway
- Article/chapterEnglish2008
Publisher, publication year, extent ...
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2008-05-21
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Wiley-Blackwell,2008
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-86926
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-86926URI
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https://doi.org/10.1111/j.1582-4934.2008.00129.xDOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (ΔTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (ΔΨm), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.
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Asoodeh, AhmadDepartment of Biophysics and Biochemistry, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran; Department of Chemistry Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
(author)
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Klonisch, ThomasDepartment of Human Anatomy and Cell Sciences, and Manitoba Institute of Child Health, Winnipeg, Canada
(author)
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Halayko, Andrew J.Department of Physiology, University of Manitoba, Winnipeg, MB, Canada; Manitoba Institute of Child Health, Winnipeg, MB, Canada
(author)
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Kadkhoda, KamranDepartment of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
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Kroczak, Tadeusz J.Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
(author)
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Gibson, Spencer B.Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; BioApplications Enterprises, Winnipeg, Canada
(author)
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Booy, Evan P.Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
(author)
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Naderi-Manesh, HosseinDepartment of Biophysics and Biochemistry, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran
(author)
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Los, Marek JanBioApplications Enterprises, Winnipeg, MB, Canada(Swepub:liu)marlo14
(author)
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Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, CanadaDepartment of Biophysics and Biochemistry, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran; Department of Chemistry Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
(creator_code:org_t)
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In:Journal of Cellular and Molecular Medicine: Wiley-Blackwell12:3, s. 1005-10221582-18381582-4934
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Ghavami, Saeid
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Asoodeh, Ahmad
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Klonisch, Thomas
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Kadkhoda, Kamran
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