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Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
A hallmark of the development of solid and hematological malignancies is the dysregulation of apoptosis, which leads to an imbalance between cell proliferation, cell survival and death. Halogenated boroxine [K(2)(B(3)O(3)F(4)OH)] (HB) is a derivative of cyclic anhydride of boronic acid, with reprodu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811610/ https://www.ncbi.nlm.nih.gov/pubmed/36369656 http://dx.doi.org/10.1002/2211-5463.13522 |
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author | Hadzic, Maida Sun, Yitong Tomic, Nikolina Tsirvouli, Eirini Kuiper, Martin Pojskic, Lejla |
author_facet | Hadzic, Maida Sun, Yitong Tomic, Nikolina Tsirvouli, Eirini Kuiper, Martin Pojskic, Lejla |
author_sort | Hadzic, Maida |
collection | PubMed |
description | A hallmark of the development of solid and hematological malignancies is the dysregulation of apoptosis, which leads to an imbalance between cell proliferation, cell survival and death. Halogenated boroxine [K(2)(B(3)O(3)F(4)OH)] (HB) is a derivative of cyclic anhydride of boronic acid, with reproducible anti‐tumor and anti‐proliferative effects in different cell models. Notably, these changes are observed to be more profound in tumor cells than in normal cells. Here, we investigated the underlying mechanisms through an extensive evaluation of (a) deregulated target genes and (b) their interactions and links with main apoptotic pathway genes upon treatment with an optimized concentration of HB. To provide deeper insights into the mechanism of action of HB, we performed identification, visualization, and pathway association of differentially expressed genes (DEGs) involved in regulation of apoptosis among tumor and non‐tumor cells upon HB treatment. We report that HB at a concentration of 0.2 mg·mL(−1) drives tumor cells to apoptosis, whereas non‐tumor cells are not affected. Comparison of DEG profiles, gene interactions and pathway associations suggests that the HB effect and tumor‐‘selectivity’ can be explained by Bax/Bak‐independent mitochondrial depolarization by ROS generation and TRAIL‐like activation, followed by permanent inhibition of NFκB signaling pathway specifically in tumor cells. |
format | Online Article Text |
id | pubmed-9811610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98116102023-01-05 Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro Hadzic, Maida Sun, Yitong Tomic, Nikolina Tsirvouli, Eirini Kuiper, Martin Pojskic, Lejla FEBS Open Bio Research Articles A hallmark of the development of solid and hematological malignancies is the dysregulation of apoptosis, which leads to an imbalance between cell proliferation, cell survival and death. Halogenated boroxine [K(2)(B(3)O(3)F(4)OH)] (HB) is a derivative of cyclic anhydride of boronic acid, with reproducible anti‐tumor and anti‐proliferative effects in different cell models. Notably, these changes are observed to be more profound in tumor cells than in normal cells. Here, we investigated the underlying mechanisms through an extensive evaluation of (a) deregulated target genes and (b) their interactions and links with main apoptotic pathway genes upon treatment with an optimized concentration of HB. To provide deeper insights into the mechanism of action of HB, we performed identification, visualization, and pathway association of differentially expressed genes (DEGs) involved in regulation of apoptosis among tumor and non‐tumor cells upon HB treatment. We report that HB at a concentration of 0.2 mg·mL(−1) drives tumor cells to apoptosis, whereas non‐tumor cells are not affected. Comparison of DEG profiles, gene interactions and pathway associations suggests that the HB effect and tumor‐‘selectivity’ can be explained by Bax/Bak‐independent mitochondrial depolarization by ROS generation and TRAIL‐like activation, followed by permanent inhibition of NFκB signaling pathway specifically in tumor cells. John Wiley and Sons Inc. 2022-11-22 /pmc/articles/PMC9811610/ /pubmed/36369656 http://dx.doi.org/10.1002/2211-5463.13522 Text en © 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Hadzic, Maida Sun, Yitong Tomic, Nikolina Tsirvouli, Eirini Kuiper, Martin Pojskic, Lejla Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro |
title | Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
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title_full | Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
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title_fullStr | Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
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title_full_unstemmed | Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
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title_short | Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro
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title_sort | halogenated boroxine increases propensity to apoptosis in leukemia (ut‐7) but not non‐tumor cells in vitro |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811610/ https://www.ncbi.nlm.nih.gov/pubmed/36369656 http://dx.doi.org/10.1002/2211-5463.13522 |
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