Cargando…
Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures
Arginase added to culture medium reduced arginine to negligible levels within ∼6 h, and enzyme activity persisted relatively undiminished for at least 3 days. Human and bovine arginase proved equally effective. The response of normal cells was to enter G1 (G0) arrest, from which most of the cells co...
Autores principales: | , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2003
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377179/ https://www.ncbi.nlm.nih.gov/pubmed/12592378 http://dx.doi.org/10.1038/sj.bjc.6600681 |
_version_ | 1782154795730075648 |
---|---|
author | Philip, R Campbell, E Wheatley, D N |
author_facet | Philip, R Campbell, E Wheatley, D N |
author_sort | Philip, R |
collection | PubMed |
description | Arginase added to culture medium reduced arginine to negligible levels within ∼6 h, and enzyme activity persisted relatively undiminished for at least 3 days. Human and bovine arginase proved equally effective. The response of normal cells was to enter G1 (G0) arrest, from which most of the cells could be recovered weeks later. In contrast, malignant cell lines treated with unpegylated or pegylated enzyme resulted in cell death on a massive scale within 3 – 5 days, with a very low to negligible percentage of cells (<0.01%) being recoverable on restoration with arginine. Although pegylation resulted in a 40% drop in specific activity, arginase was considerably more stable and remained active for ≫8 days. Arginine decarboxylase caused malignant cell arrest at the same units per millilitre as arginase. Its breakdown product, agmatine, was relatively nontoxic in the presence of arginine, but exacerbated cell death above millimolar concentration in its absence. Although ornithine failed to rescue cells from deprivation, citrulline recovered cells in all cases, although less well in fast-growing tumour cell populations, whereas readdition of arginine failed to work unless a complete medium change was given (because of the persistence of the enzymes in the medium catabolising its destruction). The advantages and disadvantages of these two arginine-catabolising enzymes are discussed, and compared with arginine deiminase. |
format | Text |
id | pubmed-2377179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23771792009-09-10 Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures Philip, R Campbell, E Wheatley, D N Br J Cancer Experimental Therapeutics Arginase added to culture medium reduced arginine to negligible levels within ∼6 h, and enzyme activity persisted relatively undiminished for at least 3 days. Human and bovine arginase proved equally effective. The response of normal cells was to enter G1 (G0) arrest, from which most of the cells could be recovered weeks later. In contrast, malignant cell lines treated with unpegylated or pegylated enzyme resulted in cell death on a massive scale within 3 – 5 days, with a very low to negligible percentage of cells (<0.01%) being recoverable on restoration with arginine. Although pegylation resulted in a 40% drop in specific activity, arginase was considerably more stable and remained active for ≫8 days. Arginine decarboxylase caused malignant cell arrest at the same units per millilitre as arginase. Its breakdown product, agmatine, was relatively nontoxic in the presence of arginine, but exacerbated cell death above millimolar concentration in its absence. Although ornithine failed to rescue cells from deprivation, citrulline recovered cells in all cases, although less well in fast-growing tumour cell populations, whereas readdition of arginine failed to work unless a complete medium change was given (because of the persistence of the enzymes in the medium catabolising its destruction). The advantages and disadvantages of these two arginine-catabolising enzymes are discussed, and compared with arginine deiminase. Nature Publishing Group 2003-02-24 2003-02-18 /pmc/articles/PMC2377179/ /pubmed/12592378 http://dx.doi.org/10.1038/sj.bjc.6600681 Text en Copyright © 2003 Cancer Research UK 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 | Experimental Therapeutics Philip, R Campbell, E Wheatley, D N Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title | Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title_full | Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title_fullStr | Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title_full_unstemmed | Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title_short | Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures |
title_sort | arginine deprivation, growth inhibition and tumour cell death: 2. enzymatic degradation of arginine in normal and malignant cell cultures |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377179/ https://www.ncbi.nlm.nih.gov/pubmed/12592378 http://dx.doi.org/10.1038/sj.bjc.6600681 |
work_keys_str_mv | AT philipr argininedeprivationgrowthinhibitionandtumourcelldeath2enzymaticdegradationofarginineinnormalandmalignantcellcultures AT campbelle argininedeprivationgrowthinhibitionandtumourcelldeath2enzymaticdegradationofarginineinnormalandmalignantcellcultures AT wheatleydn argininedeprivationgrowthinhibitionandtumourcelldeath2enzymaticdegradationofarginineinnormalandmalignantcellcultures |