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Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

The effects of arginine deprivation (–Arg) has been examined in 26 cell lines. Less than 10% of those with transformed or malignant phenotype survived for > 5 days, and many died more rapidly, notably leukaemic cells. Bivariate flow cytometry confirmed that vulnerable cell lines failed to move ou...

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Autores principales: Scott, L, Lamb, J, Smith, S, Wheatley, D N
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363527/
https://www.ncbi.nlm.nih.gov/pubmed/10952786
http://dx.doi.org/10.1054/bjoc.2000.1353
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author Scott, L
Lamb, J
Smith, S
Wheatley, D N
author_facet Scott, L
Lamb, J
Smith, S
Wheatley, D N
author_sort Scott, L
collection PubMed
description The effects of arginine deprivation (–Arg) has been examined in 26 cell lines. Less than 10% of those with transformed or malignant phenotype survived for > 5 days, and many died more rapidly, notably leukaemic cells. Bivariate flow cytometry confirmed that vulnerable cell lines failed to move out of cell cycle into a quiescent state (G0), but reinitiated DNA synthesis. Many cells remained in S-phase, and/or had difficulty progressing through to G2 and M. Two tumour lines proved relatively ‘resistant’, A549 and MCF7. Although considerable cell loss occurred initially, both lines showed a ‘cell cycle freeze’, in which cells survived for > 10 days. These cells recovered their proliferative activity in +Arg medium, but behaved in the same manner to a second –Arg episode as they did to the first episode. In contrast, normal cells entered G0 and survived in –Arg medium for several weeks, with the majority of cells recovering with predictable kinetics in +Arg medium. In general, cells from a wide range of tumours and established lines die quickly in vitro following –Arg treatment, because of defective cell cycle checkpoint stringency, the efficacy of the treatment being most clearly demonstrated in co-cultures in which only the normal cells survived. The findings demonstrate a potentially simple, effective and non-genotoxic strategy for the treatment of a wide range of cancers. © 2000 Cancer Research Campaign
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spelling pubmed-23635272009-09-10 Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells Scott, L Lamb, J Smith, S Wheatley, D N Br J Cancer Regular Article The effects of arginine deprivation (–Arg) has been examined in 26 cell lines. Less than 10% of those with transformed or malignant phenotype survived for > 5 days, and many died more rapidly, notably leukaemic cells. Bivariate flow cytometry confirmed that vulnerable cell lines failed to move out of cell cycle into a quiescent state (G0), but reinitiated DNA synthesis. Many cells remained in S-phase, and/or had difficulty progressing through to G2 and M. Two tumour lines proved relatively ‘resistant’, A549 and MCF7. Although considerable cell loss occurred initially, both lines showed a ‘cell cycle freeze’, in which cells survived for > 10 days. These cells recovered their proliferative activity in +Arg medium, but behaved in the same manner to a second –Arg episode as they did to the first episode. In contrast, normal cells entered G0 and survived in –Arg medium for several weeks, with the majority of cells recovering with predictable kinetics in +Arg medium. In general, cells from a wide range of tumours and established lines die quickly in vitro following –Arg treatment, because of defective cell cycle checkpoint stringency, the efficacy of the treatment being most clearly demonstrated in co-cultures in which only the normal cells survived. The findings demonstrate a potentially simple, effective and non-genotoxic strategy for the treatment of a wide range of cancers. © 2000 Cancer Research Campaign Nature Publishing Group 2000-09 2000-08-17 /pmc/articles/PMC2363527/ /pubmed/10952786 http://dx.doi.org/10.1054/bjoc.2000.1353 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Scott, L
Lamb, J
Smith, S
Wheatley, D N
Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title_full Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title_fullStr Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title_full_unstemmed Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title_short Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
title_sort single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363527/
https://www.ncbi.nlm.nih.gov/pubmed/10952786
http://dx.doi.org/10.1054/bjoc.2000.1353
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