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Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL),...

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Autores principales: Fetisov, Timur I., Borunova, Anna A., Antipova, Alina S., Antoshina, Elena E., Trukhanova, Lubov S., Gorkova, Tatyana G., Zuevskaya, Svetlana N., Maslov, Alexei, Gurova, Katerina, Gudkov, Andrei, Lesovaya, Ekaterina A., Belitsky, Gennady A., Yakubovskaya, Marianna G., Kirsanov, Kirill I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856019/
https://www.ncbi.nlm.nih.gov/pubmed/36672738
http://dx.doi.org/10.3390/biomedicines11010230
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author Fetisov, Timur I.
Borunova, Anna A.
Antipova, Alina S.
Antoshina, Elena E.
Trukhanova, Lubov S.
Gorkova, Tatyana G.
Zuevskaya, Svetlana N.
Maslov, Alexei
Gurova, Katerina
Gudkov, Andrei
Lesovaya, Ekaterina A.
Belitsky, Gennady A.
Yakubovskaya, Marianna G.
Kirsanov, Kirill I.
author_facet Fetisov, Timur I.
Borunova, Anna A.
Antipova, Alina S.
Antoshina, Elena E.
Trukhanova, Lubov S.
Gorkova, Tatyana G.
Zuevskaya, Svetlana N.
Maslov, Alexei
Gurova, Katerina
Gudkov, Andrei
Lesovaya, Ekaterina A.
Belitsky, Gennady A.
Yakubovskaya, Marianna G.
Kirsanov, Kirill I.
author_sort Fetisov, Timur I.
collection PubMed
description The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137’s cytostatic effect comparatively to other hematological malignancy cells. Flow cytometry cell cycle analysis revealed an increase in subG1 and G2/M populations after CBL0137 cell treatment, but the prevalent type of arrest varied. Apoptosis activation by CBL0137 measured by Annexin-V/PI dual staining was more active in AML and MM cells. RT2 PCR array showed that changes caused by CBL0137 in signaling pathways involved in cancer pathogenesis were more intensive in AML and MM cells. On the murine model of AML WEHI-3, CBL0137 showed significant anticancer effects in vivo, which were evaluated by corresponding changes in spleen and liver. Thus, more pronounced anticancer effects of CBL0137 in vitro were observed in respect to AML and MM. Experiments in vivo also indicated the perspective of CBL0137 use for AML treatment. This in accordance with the frontline treatment approach in AML using epigenetic drugs.
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spelling pubmed-98560192023-01-21 Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo Fetisov, Timur I. Borunova, Anna A. Antipova, Alina S. Antoshina, Elena E. Trukhanova, Lubov S. Gorkova, Tatyana G. Zuevskaya, Svetlana N. Maslov, Alexei Gurova, Katerina Gudkov, Andrei Lesovaya, Ekaterina A. Belitsky, Gennady A. Yakubovskaya, Marianna G. Kirsanov, Kirill I. Biomedicines Article The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137’s cytostatic effect comparatively to other hematological malignancy cells. Flow cytometry cell cycle analysis revealed an increase in subG1 and G2/M populations after CBL0137 cell treatment, but the prevalent type of arrest varied. Apoptosis activation by CBL0137 measured by Annexin-V/PI dual staining was more active in AML and MM cells. RT2 PCR array showed that changes caused by CBL0137 in signaling pathways involved in cancer pathogenesis were more intensive in AML and MM cells. On the murine model of AML WEHI-3, CBL0137 showed significant anticancer effects in vivo, which were evaluated by corresponding changes in spleen and liver. Thus, more pronounced anticancer effects of CBL0137 in vitro were observed in respect to AML and MM. Experiments in vivo also indicated the perspective of CBL0137 use for AML treatment. This in accordance with the frontline treatment approach in AML using epigenetic drugs. MDPI 2023-01-16 /pmc/articles/PMC9856019/ /pubmed/36672738 http://dx.doi.org/10.3390/biomedicines11010230 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fetisov, Timur I.
Borunova, Anna A.
Antipova, Alina S.
Antoshina, Elena E.
Trukhanova, Lubov S.
Gorkova, Tatyana G.
Zuevskaya, Svetlana N.
Maslov, Alexei
Gurova, Katerina
Gudkov, Andrei
Lesovaya, Ekaterina A.
Belitsky, Gennady A.
Yakubovskaya, Marianna G.
Kirsanov, Kirill I.
Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title_full Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title_fullStr Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title_full_unstemmed Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title_short Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
title_sort targeting features of curaxin cbl0137 on hematological malignancies in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856019/
https://www.ncbi.nlm.nih.gov/pubmed/36672738
http://dx.doi.org/10.3390/biomedicines11010230
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