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Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectivel...

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Autores principales: You, Hongliang, Wang, Dao, Wei, Linlin, Chen, Jiao, Li, Huanhuan, Liu, Yufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885176/
https://www.ncbi.nlm.nih.gov/pubmed/35237325
http://dx.doi.org/10.1155/2022/8281267
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author You, Hongliang
Wang, Dao
Wei, Linlin
Chen, Jiao
Li, Huanhuan
Liu, Yufeng
author_facet You, Hongliang
Wang, Dao
Wei, Linlin
Chen, Jiao
Li, Huanhuan
Liu, Yufeng
author_sort You, Hongliang
collection PubMed
description Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectively decreased the concentration of intracellular iron in ALL cells. DFO inhibited proliferation, induced apoptosis, and obstructed cell cycle of ALL cells, whereas DFO and dextriferron (Dex) used in combination significantly decreased the sensitivity of ALL cells to DFO. Reactive oxygen species (ROS) level was reduced in ALL cells treated with DFO, and the combination of DFO and Dex reversed the effects of DFO. In vivo, DFO inhibited mouse tumor growth. Besides, cyclinD1, β-catenin, c-Myc, hypoxia inducible factor 1 (HIF-1), p-p38MAPK, and p-ERK1/2 protein levels were significantly downregulated, and the levels of prolyl hydroxylase-2 (PHD-2) were upregulated after treated with DFO, whereas Dex treatment reversed those in vivo and in vitro. In conclusion, DFO inhibited the proliferation and ALL xenograft tumor growth, obstructed the cell cycle, and induced apoptosis of ALL cells, probably via inactivating the ROS/HIF-1α, Wnt/β-catenin, and p38MAPK/ERK signaling.
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spelling pubmed-88851762022-03-01 Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways You, Hongliang Wang, Dao Wei, Linlin Chen, Jiao Li, Huanhuan Liu, Yufeng J Oncol Research Article Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectively decreased the concentration of intracellular iron in ALL cells. DFO inhibited proliferation, induced apoptosis, and obstructed cell cycle of ALL cells, whereas DFO and dextriferron (Dex) used in combination significantly decreased the sensitivity of ALL cells to DFO. Reactive oxygen species (ROS) level was reduced in ALL cells treated with DFO, and the combination of DFO and Dex reversed the effects of DFO. In vivo, DFO inhibited mouse tumor growth. Besides, cyclinD1, β-catenin, c-Myc, hypoxia inducible factor 1 (HIF-1), p-p38MAPK, and p-ERK1/2 protein levels were significantly downregulated, and the levels of prolyl hydroxylase-2 (PHD-2) were upregulated after treated with DFO, whereas Dex treatment reversed those in vivo and in vitro. In conclusion, DFO inhibited the proliferation and ALL xenograft tumor growth, obstructed the cell cycle, and induced apoptosis of ALL cells, probably via inactivating the ROS/HIF-1α, Wnt/β-catenin, and p38MAPK/ERK signaling. Hindawi 2022-02-21 /pmc/articles/PMC8885176/ /pubmed/35237325 http://dx.doi.org/10.1155/2022/8281267 Text en Copyright © 2022 Hongliang You et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
You, Hongliang
Wang, Dao
Wei, Linlin
Chen, Jiao
Li, Huanhuan
Liu, Yufeng
Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title_full Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title_fullStr Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title_full_unstemmed Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title_short Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1α, Wnt/β-Catenin, and p38MAPK/ERK Pathways
title_sort deferoxamine inhibits acute lymphoblastic leukemia progression through repression of ros/hif-1α, wnt/β-catenin, and p38mapk/erk pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885176/
https://www.ncbi.nlm.nih.gov/pubmed/35237325
http://dx.doi.org/10.1155/2022/8281267
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