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Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance

Autophagy is a lysosomal degradation mechanism that is essential for cell survival, differentiation, development, and homeostasis. Autophagy protects cells from various stresses, including protecting normal cells from harmful metabolic conditions, and cancer cells from chemotherapeutics. In the curr...

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Autores principales: CHEONG, JUNE-WON, KIM, YUNDEOK, EOM, JU IN, JEUNG, HOI-KYUNG, MIN, YOO HONG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805098/
https://www.ncbi.nlm.nih.gov/pubmed/26935591
http://dx.doi.org/10.3892/mmr.2016.4949
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author CHEONG, JUNE-WON
KIM, YUNDEOK
EOM, JU IN
JEUNG, HOI-KYUNG
MIN, YOO HONG
author_facet CHEONG, JUNE-WON
KIM, YUNDEOK
EOM, JU IN
JEUNG, HOI-KYUNG
MIN, YOO HONG
author_sort CHEONG, JUNE-WON
collection PubMed
description Autophagy is a lysosomal degradation mechanism that is essential for cell survival, differentiation, development, and homeostasis. Autophagy protects cells from various stresses, including protecting normal cells from harmful metabolic conditions, and cancer cells from chemotherapeutics. In the current study, a cytarabine arabinoside (Ara-C)-sensitive U937 leukemia cell line and an Ara-C-resistant U937 (U937/AR) cell line were assessed for baseline autophagy activity by investigating the LC3-I conversion to LC3-II, performing EGFP-LC3 puncta, an acidic autophagolysosome assay, and measuring the expression of various autophagy-related genes. The results demonstrated significantly higher autophagic activity in the U937/AR cells compared with the U937 cells, when the cells were cultured with or without serum. Furthermore, an increase in the autophagic activity in starved U937/AR cells was demonstrated, compared with that in the starved U937 cells. Administration of an autophagy inhibitor demonstrated no change in cell death in the two cell lines when cultured with serum, however, it induced cell death regardless of the Ara-C sensitivity when the cell lines were cultured without serum. In addition, the U937 cells demonstrated an Ara-C resistance when cultured without serum. Co-treatment with Ara-C and the autophagy inhibitor significantly induced cell death in the U937/AR and Ara-C-sensitive U937 cells. In conclusion, autophagy serves an important role in protecting U937 cells from Ara-C and in the development of Ara-C resistance. Inhibition of autophagy combined with the Ara-C treatment in the U937 cells augmented the anti-leukemic effect of Ara-C and overcame Ara-C resistance, suggesting that autophagy may be an important therapeutic target to further improve the treatment outcome in patients with acute myeloid leukemia.
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spelling pubmed-48050982016-04-04 Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance CHEONG, JUNE-WON KIM, YUNDEOK EOM, JU IN JEUNG, HOI-KYUNG MIN, YOO HONG Mol Med Rep Articles Autophagy is a lysosomal degradation mechanism that is essential for cell survival, differentiation, development, and homeostasis. Autophagy protects cells from various stresses, including protecting normal cells from harmful metabolic conditions, and cancer cells from chemotherapeutics. In the current study, a cytarabine arabinoside (Ara-C)-sensitive U937 leukemia cell line and an Ara-C-resistant U937 (U937/AR) cell line were assessed for baseline autophagy activity by investigating the LC3-I conversion to LC3-II, performing EGFP-LC3 puncta, an acidic autophagolysosome assay, and measuring the expression of various autophagy-related genes. The results demonstrated significantly higher autophagic activity in the U937/AR cells compared with the U937 cells, when the cells were cultured with or without serum. Furthermore, an increase in the autophagic activity in starved U937/AR cells was demonstrated, compared with that in the starved U937 cells. Administration of an autophagy inhibitor demonstrated no change in cell death in the two cell lines when cultured with serum, however, it induced cell death regardless of the Ara-C sensitivity when the cell lines were cultured without serum. In addition, the U937 cells demonstrated an Ara-C resistance when cultured without serum. Co-treatment with Ara-C and the autophagy inhibitor significantly induced cell death in the U937/AR and Ara-C-sensitive U937 cells. In conclusion, autophagy serves an important role in protecting U937 cells from Ara-C and in the development of Ara-C resistance. Inhibition of autophagy combined with the Ara-C treatment in the U937 cells augmented the anti-leukemic effect of Ara-C and overcame Ara-C resistance, suggesting that autophagy may be an important therapeutic target to further improve the treatment outcome in patients with acute myeloid leukemia. D.A. Spandidos 2016-04 2016-02-29 /pmc/articles/PMC4805098/ /pubmed/26935591 http://dx.doi.org/10.3892/mmr.2016.4949 Text en Copyright: © Cheong et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
CHEONG, JUNE-WON
KIM, YUNDEOK
EOM, JU IN
JEUNG, HOI-KYUNG
MIN, YOO HONG
Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title_full Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title_fullStr Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title_full_unstemmed Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title_short Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance
title_sort enhanced autophagy in cytarabine arabinoside-resistant u937 leukemia cells and its potential as a target for overcoming resistance
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805098/
https://www.ncbi.nlm.nih.gov/pubmed/26935591
http://dx.doi.org/10.3892/mmr.2016.4949
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