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The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study.
We have used flow cytometry to study the mechanism of cytotoxic action of a series of ammine/amine Pt(IV) dicarboxylates [ammine diacetatodichloro(cyclohexylamine) platinum(IV), JM216; ammine dibutyratodichloro(cyclohexylamine)platinum(IV), JM221; ammine diacetatodichloro(propylamine)platinum(IV), J...
Autores principales: | , , , , , , |
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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/PMC2074815/ https://www.ncbi.nlm.nih.gov/pubmed/8980393 |
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author | Ormerod, M. G. Orr, R. M. O'Neill, C. F. Chwalinski, T. Titley, J. C. Kelland, L. R. Harrap, K. R. |
author_facet | Ormerod, M. G. Orr, R. M. O'Neill, C. F. Chwalinski, T. Titley, J. C. Kelland, L. R. Harrap, K. R. |
author_sort | Ormerod, M. G. |
collection | PubMed |
description | We have used flow cytometry to study the mechanism of cytotoxic action of a series of ammine/amine Pt(IV) dicarboxylates [ammine diacetatodichloro(cyclohexylamine) platinum(IV), JM216; ammine dibutyratodichloro(cyclohexylamine)platinum(IV), JM221; ammine diacetatodichloro(propylamine)platinum(IV), JM223; ammine dibenzoatodichloro(propylamine)platinum(IV), JM244]. JM216 has been shown to have clinical potential and has recently entered phase II trials. All the compounds caused a slowdown in S-phase transit followed by a block in G2. Cells died either through apoptosis (largely during S-phase) or by failing to overcome the G2 block (some days after treatment). In G2, the cells either divided or enlarged and died. At equitoxic doses, JM216 showed the most apoptotic cells and had the most platinum bound to the DNA; JM244 showed the fewest apoptotic cells and had the least platinum bound to DNA. We suggest that whether apoptosis was triggered or not was governed by the total amount of Pt bound to the DNA; the type of lesion was more important in determining whether a cell became blocked in G2. |
format | Text |
id | pubmed-2074815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1996 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20748152009-09-10 The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. Ormerod, M. G. Orr, R. M. O'Neill, C. F. Chwalinski, T. Titley, J. C. Kelland, L. R. Harrap, K. R. Br J Cancer Research Article We have used flow cytometry to study the mechanism of cytotoxic action of a series of ammine/amine Pt(IV) dicarboxylates [ammine diacetatodichloro(cyclohexylamine) platinum(IV), JM216; ammine dibutyratodichloro(cyclohexylamine)platinum(IV), JM221; ammine diacetatodichloro(propylamine)platinum(IV), JM223; ammine dibenzoatodichloro(propylamine)platinum(IV), JM244]. JM216 has been shown to have clinical potential and has recently entered phase II trials. All the compounds caused a slowdown in S-phase transit followed by a block in G2. Cells died either through apoptosis (largely during S-phase) or by failing to overcome the G2 block (some days after treatment). In G2, the cells either divided or enlarged and died. At equitoxic doses, JM216 showed the most apoptotic cells and had the most platinum bound to the DNA; JM244 showed the fewest apoptotic cells and had the least platinum bound to DNA. We suggest that whether apoptosis was triggered or not was governed by the total amount of Pt bound to the DNA; the type of lesion was more important in determining whether a cell became blocked in G2. Nature Publishing Group 1996-12 /pmc/articles/PMC2074815/ /pubmed/8980393 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 Ormerod, M. G. Orr, R. M. O'Neill, C. F. Chwalinski, T. Titley, J. C. Kelland, L. R. Harrap, K. R. The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title | The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title_full | The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title_fullStr | The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title_full_unstemmed | The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title_short | The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study. |
title_sort | cytotoxic action of four ammine/amine platinum(iv) dicarboxylates: a flow cytometric study. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074815/ https://www.ncbi.nlm.nih.gov/pubmed/8980393 |
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