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...

Descripción completa

Detalles Bibliográficos
Autores principales: Philip, R, Campbell, E, Wheatley, D N
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