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

  • Authors:
    • June‑Won Cheong
    • Yundeok Kim
    • Ju In Eom
    • Hoi‑Kyung Jeung
    • Yoo Hong Min
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120‑752, Republic of Korea, Medical Research Center, Yonsei University College of Medicine, Seoul 120‑752, Republic of Korea
    Copyright: © Cheong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3433-3440
    |
    Published online on: February 29, 2016
       https://doi.org/10.3892/mmr.2016.4949
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Cheong JW, Kim Y, Eom JI, Jeung HK and Min YH: Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance. Mol Med Rep 13: 3433-3440, 2016.
APA
Cheong, J., Kim, Y., Eom, J.I., Jeung, H., & Min, Y.H. (2016). Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance. Molecular Medicine Reports, 13, 3433-3440. https://doi.org/10.3892/mmr.2016.4949
MLA
Cheong, J., Kim, Y., Eom, J. I., Jeung, H., Min, Y. H."Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance". Molecular Medicine Reports 13.4 (2016): 3433-3440.
Chicago
Cheong, J., Kim, Y., Eom, J. I., Jeung, H., Min, Y. H."Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance". Molecular Medicine Reports 13, no. 4 (2016): 3433-3440. https://doi.org/10.3892/mmr.2016.4949
Copy and paste a formatted citation
x
Spandidos Publications style
Cheong JW, Kim Y, Eom JI, Jeung HK and Min YH: Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance. Mol Med Rep 13: 3433-3440, 2016.
APA
Cheong, J., Kim, Y., Eom, J.I., Jeung, H., & Min, Y.H. (2016). Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance. Molecular Medicine Reports, 13, 3433-3440. https://doi.org/10.3892/mmr.2016.4949
MLA
Cheong, J., Kim, Y., Eom, J. I., Jeung, H., Min, Y. H."Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance". Molecular Medicine Reports 13.4 (2016): 3433-3440.
Chicago
Cheong, J., Kim, Y., Eom, J. I., Jeung, H., Min, Y. H."Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance". Molecular Medicine Reports 13, no. 4 (2016): 3433-3440. https://doi.org/10.3892/mmr.2016.4949
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