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Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway
Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
Department 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 .
Department of Human Anatomy and Cell Sciences, and Manitoba Institute of Child Health, Winnipeg, Canada.
Department of Physiology, University of Manitoba, Winnipeg, MB, Canada; Manitoba Institute of Child Health, Winnipeg, MB, Canada.
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2008 (English)In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, Vol. 12, no 3, 1005-1022 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2008. Vol. 12, no 3, 1005-1022 p.
Keyword [en]
antibacterial peptide; defensin; Brevinin-2R; cell death; caspase activation; lysosomotrophic agent; late and early endosome; ROS; mitochondrial pathway; targetted cancer therapy
National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology Biochemistry and Molecular Biology
URN: urn:nbn:se:liu:diva-86926DOI: 10.1111/j.1582-4934.2008.00129.xISI: 000256105200020OAI: diva2:583302
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2013-09-03

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Los, Marek Jan
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Journal of Cellular and Molecular Medicine (Print)
Cancer and OncologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cell BiologyBiochemistry and Molecular Biology

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