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Comparison of in vitro antileukemic activity of obatoclax and ABT-737
Obatoclax and ABT-737 belong to a new class of anticancer agents known as BH3-mimetics. These agents antagonize the anti-apoptotic members of Bcl-2 family. The Bcl-2 proteins modulate sensitivity of many types of cancer cells to chemotherapy. Therefore, the objective of the present study was to exam...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999481/ https://www.ncbi.nlm.nih.gov/pubmed/26880588 http://dx.doi.org/10.1007/s13277-016-4943-z |
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author | Opydo-Chanek, Małgorzata Mazur, Lidia |
author_facet | Opydo-Chanek, Małgorzata Mazur, Lidia |
author_sort | Opydo-Chanek, Małgorzata |
collection | PubMed |
description | Obatoclax and ABT-737 belong to a new class of anticancer agents known as BH3-mimetics. These agents antagonize the anti-apoptotic members of Bcl-2 family. The Bcl-2 proteins modulate sensitivity of many types of cancer cells to chemotherapy. Therefore, the objective of the present study was to examine and compare the antileukemic activity of obatoclax and ABT-737 applied alone, and in combination with anticancer agent, mafosfamide and daunorubicin. The in vitro cytotoxic effects of the tested agents on human leukemia cells were determined using the spectrophotometric MTT test, Coulter electrical impedance method, flow cytometry annexin V–fluorescein/propidium iodide assay, and light microscopy technique. The combination index analysis was used to quantify the extent of agent interactions. BH3 mimetics significantly decreased the leukemia cell viability and synergistically enhanced the cytotoxic effects induced by mafosfamide and daunorubicin. Obatoclax affected the cell viability to a greater degree than did ABT-737. In addition, various patterns of temporary changes in the cell volume and count, and in the frequency of leukemia cells undergoing apoptosis, were found 24 and 48 h after the tested agent application. ABT-737 combined with anticancer agents induced apoptosis more effectively than obatoclax when given in the same combination regimen. The results of the present study point to the different antileukemic activities of obatoclax and ABT-737, when applied alone, and in combination with anticancer agents. A better understanding of the exact mechanisms of BH3 mimetic action is of key importance for their optional use in cancer therapy. |
format | Online Article Text |
id | pubmed-4999481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-49994812016-09-12 Comparison of in vitro antileukemic activity of obatoclax and ABT-737 Opydo-Chanek, Małgorzata Mazur, Lidia Tumour Biol Original Article Obatoclax and ABT-737 belong to a new class of anticancer agents known as BH3-mimetics. These agents antagonize the anti-apoptotic members of Bcl-2 family. The Bcl-2 proteins modulate sensitivity of many types of cancer cells to chemotherapy. Therefore, the objective of the present study was to examine and compare the antileukemic activity of obatoclax and ABT-737 applied alone, and in combination with anticancer agent, mafosfamide and daunorubicin. The in vitro cytotoxic effects of the tested agents on human leukemia cells were determined using the spectrophotometric MTT test, Coulter electrical impedance method, flow cytometry annexin V–fluorescein/propidium iodide assay, and light microscopy technique. The combination index analysis was used to quantify the extent of agent interactions. BH3 mimetics significantly decreased the leukemia cell viability and synergistically enhanced the cytotoxic effects induced by mafosfamide and daunorubicin. Obatoclax affected the cell viability to a greater degree than did ABT-737. In addition, various patterns of temporary changes in the cell volume and count, and in the frequency of leukemia cells undergoing apoptosis, were found 24 and 48 h after the tested agent application. ABT-737 combined with anticancer agents induced apoptosis more effectively than obatoclax when given in the same combination regimen. The results of the present study point to the different antileukemic activities of obatoclax and ABT-737, when applied alone, and in combination with anticancer agents. A better understanding of the exact mechanisms of BH3 mimetic action is of key importance for their optional use in cancer therapy. Springer Netherlands 2016-02-15 /pmc/articles/PMC4999481/ /pubmed/26880588 http://dx.doi.org/10.1007/s13277-016-4943-z Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Original Article Opydo-Chanek, Małgorzata Mazur, Lidia Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title | Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title_full | Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title_fullStr | Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title_full_unstemmed | Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title_short | Comparison of in vitro antileukemic activity of obatoclax and ABT-737 |
title_sort | comparison of in vitro antileukemic activity of obatoclax and abt-737 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999481/ https://www.ncbi.nlm.nih.gov/pubmed/26880588 http://dx.doi.org/10.1007/s13277-016-4943-z |
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