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Inhibition of tumour growth by lipoxygenase inhibitors.
The potential involvement of lipoxygenase metabolites in the tumour growth stimulatory activity of arachidonic and linoleic acid has been studied using the 5-lipoxygenase inhibitors, BWA4C, BWB70C and Zileuton. In vitro the former two agents were relatively potent inhibitors of growth of murine aden...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1996
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074717/ https://www.ncbi.nlm.nih.gov/pubmed/8795568 |
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author | Hussey, H. J. Tisdale, M. J. |
author_facet | Hussey, H. J. Tisdale, M. J. |
author_sort | Hussey, H. J. |
collection | PubMed |
description | The potential involvement of lipoxygenase metabolites in the tumour growth stimulatory activity of arachidonic and linoleic acid has been studied using the 5-lipoxygenase inhibitors, BWA4C, BWB70C and Zileuton. In vitro the former two agents were relatively potent inhibitors of growth of murine adenocarcinomas (MACs) with IC50 values < 10 microM, whereas Zileuton was less effective. In vivo studies showed BWA4C to be an effective inhibitor of the growth of both the MAC26 and MAC16 tumours at dose levels between 5 and 25 mg kg-1 (b.d.). The growth rate of the MAC26 tumour was also decreased by BWB70C at 25 mg kg-1, whereas lower doses were either ineffective or stimulated tumour growth. This differential effect of the 5-lipoxygenases inhibitors on tumour growth may arise from effects on the 12- and 15-lipoxygenase pathways. To quantify the effect cells were labelled with [3H]arachidonic acid and the biosynthesis of 5-, 12- and 15-hydroxyeicosatetraenoic acid (HETE) was analysed by high-performance liquid chromatography. All three agents caused a decrease in 5-HETE production, although the effect was less pronounced with Zileuton. In MAC26 cells both BWA4C and BWB70C caused a decrease in 12-HETE formation whereas Zileuton had no effect on the other lipoxygenase pathways. The inhibitory effect of these agents on cell growth may result from an imbalance of metabolism of arachidonic acid between the 5-, 12- and 15-lipoxygenase pathways. |
format | Text |
id | pubmed-2074717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1996 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20747172009-09-10 Inhibition of tumour growth by lipoxygenase inhibitors. Hussey, H. J. Tisdale, M. J. Br J Cancer Research Article The potential involvement of lipoxygenase metabolites in the tumour growth stimulatory activity of arachidonic and linoleic acid has been studied using the 5-lipoxygenase inhibitors, BWA4C, BWB70C and Zileuton. In vitro the former two agents were relatively potent inhibitors of growth of murine adenocarcinomas (MACs) with IC50 values < 10 microM, whereas Zileuton was less effective. In vivo studies showed BWA4C to be an effective inhibitor of the growth of both the MAC26 and MAC16 tumours at dose levels between 5 and 25 mg kg-1 (b.d.). The growth rate of the MAC26 tumour was also decreased by BWB70C at 25 mg kg-1, whereas lower doses were either ineffective or stimulated tumour growth. This differential effect of the 5-lipoxygenases inhibitors on tumour growth may arise from effects on the 12- and 15-lipoxygenase pathways. To quantify the effect cells were labelled with [3H]arachidonic acid and the biosynthesis of 5-, 12- and 15-hydroxyeicosatetraenoic acid (HETE) was analysed by high-performance liquid chromatography. All three agents caused a decrease in 5-HETE production, although the effect was less pronounced with Zileuton. In MAC26 cells both BWA4C and BWB70C caused a decrease in 12-HETE formation whereas Zileuton had no effect on the other lipoxygenase pathways. The inhibitory effect of these agents on cell growth may result from an imbalance of metabolism of arachidonic acid between the 5-, 12- and 15-lipoxygenase pathways. Nature Publishing Group 1996-09 /pmc/articles/PMC2074717/ /pubmed/8795568 Text en 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 | Research Article Hussey, H. J. Tisdale, M. J. Inhibition of tumour growth by lipoxygenase inhibitors. |
title | Inhibition of tumour growth by lipoxygenase inhibitors. |
title_full | Inhibition of tumour growth by lipoxygenase inhibitors. |
title_fullStr | Inhibition of tumour growth by lipoxygenase inhibitors. |
title_full_unstemmed | Inhibition of tumour growth by lipoxygenase inhibitors. |
title_short | Inhibition of tumour growth by lipoxygenase inhibitors. |
title_sort | inhibition of tumour growth by lipoxygenase inhibitors. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074717/ https://www.ncbi.nlm.nih.gov/pubmed/8795568 |
work_keys_str_mv | AT husseyhj inhibitionoftumourgrowthbylipoxygenaseinhibitors AT tisdalemj inhibitionoftumourgrowthbylipoxygenaseinhibitors |