Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway
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
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.
antibacterial peptide; defensin; Brevinin-2R; cell death; caspase activation; lysosomotrophic agent; late and early endosome; ROS; mitochondrial pathway; targetted cancer therapy
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
IdentifiersURN: urn:nbn:se:liu:diva-86926DOI: 10.1111/j.1582-4934.2008.00129.xISI: 000256105200020OAI: oai:DiVA.org:liu-86926DiVA: diva2:583302