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The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mor...

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Autores principales: Woźniak, Marta, Makuch, Sebastian, Pastuch-Gawołek, Gabriela, Wiśniewski, Jerzy, Szeja, Wiesław, Nowak, Martyna, Krawczyk, Monika, Agrawal, Siddarth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123764/
https://www.ncbi.nlm.nih.gov/pubmed/33925555
http://dx.doi.org/10.3390/molecules26092547
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author Woźniak, Marta
Makuch, Sebastian
Pastuch-Gawołek, Gabriela
Wiśniewski, Jerzy
Szeja, Wiesław
Nowak, Martyna
Krawczyk, Monika
Agrawal, Siddarth
author_facet Woźniak, Marta
Makuch, Sebastian
Pastuch-Gawołek, Gabriela
Wiśniewski, Jerzy
Szeja, Wiesław
Nowak, Martyna
Krawczyk, Monika
Agrawal, Siddarth
author_sort Woźniak, Marta
collection PubMed
description Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients’ life. Therefore, novel targeted therapies based on the malignant cells’ common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose–methotrexate conjugate (Glu–MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu–MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu–MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients’ outcomes.
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spelling pubmed-81237642021-05-16 The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines Woźniak, Marta Makuch, Sebastian Pastuch-Gawołek, Gabriela Wiśniewski, Jerzy Szeja, Wiesław Nowak, Martyna Krawczyk, Monika Agrawal, Siddarth Molecules Article Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients’ life. Therefore, novel targeted therapies based on the malignant cells’ common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose–methotrexate conjugate (Glu–MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu–MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu–MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients’ outcomes. MDPI 2021-04-27 /pmc/articles/PMC8123764/ /pubmed/33925555 http://dx.doi.org/10.3390/molecules26092547 Text en © 2021 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
Woźniak, Marta
Makuch, Sebastian
Pastuch-Gawołek, Gabriela
Wiśniewski, Jerzy
Szeja, Wiesław
Nowak, Martyna
Krawczyk, Monika
Agrawal, Siddarth
The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title_full The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title_fullStr The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title_full_unstemmed The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title_short The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
title_sort effect of a new glucose–methotrexate conjugate on acute lymphoblastic leukemia and non-hodgkin’s lymphoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123764/
https://www.ncbi.nlm.nih.gov/pubmed/33925555
http://dx.doi.org/10.3390/molecules26092547
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