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The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis
Blast crisis (BC) is an outcome that arises during the treatment process of chronic myeloid leukemia (CML), which is possibly attained by the dysregulation of the Notch and Ikaros signaling pathways, BCR-ABL translocation, redox, and inflammatory factors. This study demonstrated that biotherapeutic...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Carol Davila University Press
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262277/ https://www.ncbi.nlm.nih.gov/pubmed/35815090 http://dx.doi.org/10.25122/jml-2021-0230 |
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author | Singh, Vivek Singh, Ranjana Mahdi, Abbas Ali Tripathi, Anil Kumar |
author_facet | Singh, Vivek Singh, Ranjana Mahdi, Abbas Ali Tripathi, Anil Kumar |
author_sort | Singh, Vivek |
collection | PubMed |
description | Blast crisis (BC) is an outcome that arises during the treatment process of chronic myeloid leukemia (CML), which is possibly attained by the dysregulation of the Notch and Ikaros signaling pathways, BCR-ABL translocation, redox, and inflammatory factors. This study demonstrated that biotherapeutic agents target aberrant molecular axis in CML-BC cells. The HALOA complex was synthesized by simple mixing of apo α-lactalbumin with oleic acid, which manages to inhibit BCR-ABL (b3a2 in K562 cells) translocation. It elevates the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and protein carbonyl, which induces DNA fragmentation in K562 cells but not in NIH cells. The complex manages to reduce the toxicity surrounding apoptotic cells by enhancing the production of superoxide dismutase (SOD) and the total antioxidant level. The HALOA complex increases leptin to maintain normoxic conditions, ultimately preventing angiogenesis. This complex downregulates the expression of IL-8 and MMP-9 and elevates the expression levels of Notch 4, Ikaros, and integrin alpha-D/CD-11d (tumor-suppressive), which conjointly prevents inflammation, metastasis, and epithelial-mesenchymal transition (EMT) in CML cells. Meanwhile, the complex downregulates Notch 1 and 2 (oncogenic), consequently inducing anoikis in CML cells. Overall, the HALOA complex shows credibility by targeting the combined molecular factors responsible for the pathogenesis of the disease and will also help to overcome MDR conditions in leukemia. |
format | Online Article Text |
id | pubmed-9262277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Carol Davila University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92622772022-07-08 The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis Singh, Vivek Singh, Ranjana Mahdi, Abbas Ali Tripathi, Anil Kumar J Med Life Original Article Blast crisis (BC) is an outcome that arises during the treatment process of chronic myeloid leukemia (CML), which is possibly attained by the dysregulation of the Notch and Ikaros signaling pathways, BCR-ABL translocation, redox, and inflammatory factors. This study demonstrated that biotherapeutic agents target aberrant molecular axis in CML-BC cells. The HALOA complex was synthesized by simple mixing of apo α-lactalbumin with oleic acid, which manages to inhibit BCR-ABL (b3a2 in K562 cells) translocation. It elevates the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and protein carbonyl, which induces DNA fragmentation in K562 cells but not in NIH cells. The complex manages to reduce the toxicity surrounding apoptotic cells by enhancing the production of superoxide dismutase (SOD) and the total antioxidant level. The HALOA complex increases leptin to maintain normoxic conditions, ultimately preventing angiogenesis. This complex downregulates the expression of IL-8 and MMP-9 and elevates the expression levels of Notch 4, Ikaros, and integrin alpha-D/CD-11d (tumor-suppressive), which conjointly prevents inflammation, metastasis, and epithelial-mesenchymal transition (EMT) in CML cells. Meanwhile, the complex downregulates Notch 1 and 2 (oncogenic), consequently inducing anoikis in CML cells. Overall, the HALOA complex shows credibility by targeting the combined molecular factors responsible for the pathogenesis of the disease and will also help to overcome MDR conditions in leukemia. Carol Davila University Press 2022-05 /pmc/articles/PMC9262277/ /pubmed/35815090 http://dx.doi.org/10.25122/jml-2021-0230 Text en © 2022 JOURNAL of MEDICINE and LIFE https://creativecommons.org/licenses/by/3.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Original Article Singh, Vivek Singh, Ranjana Mahdi, Abbas Ali Tripathi, Anil Kumar The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title | The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title_full | The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title_fullStr | The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title_full_unstemmed | The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title_short | The bioengineered HALOA complex induces anoikis in chronic myeloid leukemia cells by targeting the BCR-ABL/Notch/Ikaros/Redox/Inflammation axis |
title_sort | bioengineered haloa complex induces anoikis in chronic myeloid leukemia cells by targeting the bcr-abl/notch/ikaros/redox/inflammation axis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262277/ https://www.ncbi.nlm.nih.gov/pubmed/35815090 http://dx.doi.org/10.25122/jml-2021-0230 |
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