Journal of Cellular and Molecular Medicine, ( ISI ), Volume (12), No (3), Year (2008-2) , Pages (1005-1022)

Title : Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway. ( Brevinin-2R semi-selectively kills )

Authors: Saeid Ghavami , Ahmad Asoodeh , Thomas Klonisch , Andrew J. Halayko , Kamran Kadkhoda , Tadeusz J. Kroczak , Spencer B. Gibson , Evan P. Booy , Hossein Naderi-Manesh , Marek Los ,

Citation: BibTeX | EndNote

Brevinin-2R is a novel non-hemolytic defensin that we 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 over-expressing 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 lysosomal-mitochondrial death pathway, and involves autophagy-like cell death.

Keywords

, پپتید ضد باکتریایی, دفنسین, بروینین- 2ر, مرگ سلول, فعال سازی کاسپاز, گونه های فعال اکسیژن, مسیر
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@article{paperid:1004189,
author = {Saeid Ghavami and Asoodeh, Ahmad and Thomas Klonisch and Andrew J. Halayko and Kamran Kadkhoda and Tadeusz J. Kroczak and Spencer B. Gibson and Evan P. Booy and Hossein Naderi-Manesh and Marek Los},
title = {Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway.},
journal = {Journal of Cellular and Molecular Medicine},
year = {2008},
volume = {12},
number = {3},
month = {February},
issn = {1582-1838},
pages = {1005--1022},
numpages = {17},
keywords = {پپتید ضد باکتریایی، دفنسین، بروینین- 2ر، مرگ سلول، فعال سازی کاسپاز، گونه های فعال اکسیژن، مسیر میتوکندریایی},
}

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%0 Journal Article
%T Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway.
%A Saeid Ghavami
%A Asoodeh, Ahmad
%A Thomas Klonisch
%A Andrew J. Halayko
%A Kamran Kadkhoda
%A Tadeusz J. Kroczak
%A Spencer B. Gibson
%A Evan P. Booy
%A Hossein Naderi-Manesh
%A Marek Los
%J Journal of Cellular and Molecular Medicine
%@ 1582-1838
%D 2008

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