Effect of bovine dialyzable leukocyte extract on induction of cell differentiation and death in K562 human chronic myelogenous leukemia cells

Sierra‑Rivera,Crystel A.; Franco‑Molina,Moisés A.; Mendoza‑Gamboa,Edgar; Zapata‑Benavides,Pablo; Santaolalla‑Tapia,Jesús; Coronado‑Cerda,Erika E.; Tamez‑Guerra,Reyes S.; Rodríguez‑Padilla,Cristina

doi:10.3892/ol.2016.5285

December-2016 Volume 12 Issue 6

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December-2016 Volume 12 Issue 6

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Article Open Access

Effect of bovine dialyzable leukocyte extract on induction of cell differentiation and death in K562 human chronic myelogenous leukemia cells

Authors:
- Crystel A. Sierra‑Rivera
- Moisés A. Franco‑Molina
- Edgar Mendoza‑Gamboa
- Pablo Zapata‑Benavides
- Jesús Santaolalla‑Tapia
- Erika E. Coronado‑Cerda
- Reyes S. Tamez‑Guerra
- Cristina Rodríguez‑Padilla
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Affiliations: Laboratory of Immunology and Virology, Faculty of Biological Sciences, University Autonomous of Nuevo León (UANL), San Nicolás de los Garza, Nuevo León 66450, Mexico, Laboratory of Stem Cell Biology, Faculty of Medicine, University Autonomous of Morelos, Cuernavaca, Morelos 62350, Mexico

Copyright: © Sierra‑Rivera et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 4449-4460
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Published online on: October 18, 2016

https://doi.org/10.3892/ol.2016.5285
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Abstract

Differentiation induction therapy is an attractive approach in leukemia treatment due to the fact that in blast crisis stage, leukemic cells lose their differentiation capacity. Therefore, it has been proposed as a therapeutic strategy to induce terminal differentiation of leukemic blast cells into a specific lineage, leading to prevention of high proliferation rates. The aim of the present study was to demonstrate the potential of cell differentiation and death induced by bovine dialyzable leukocyte extract (bDLE) in the K562 cell line. For this purpose K562 and MOLT‑3 human leukemic cell lines and primary human monocytes and murine peritoneal macrophages were exposed to bDLE, phorbol myristate acetate (PMA) and dimethyl sulfoxide for 96 h, and the viability, proliferation and cell cycle were evaluated. To determine the lineage that led to cell differentiation, Romanowsky staining was performed to observe the morphological changes following the treatments, and the expression of the surface markers cluster of differentiation (CD)14+, CD68+, CD163+ and CD42a+, as well as the phagocytic activity, and the production of nitric oxide (NO) (assessed by colorimetric assay), cytokines [interleukin (IL)‑1β, IL‑6, IL‑8 and tumor necrosis factor‑α] and chemokines [chemokine (C‑C motif) ligand (CCL)2, CCL5 and chemokine (C‑X‑C motif) ligand 8] in cell supernatants was assessed by flow cytometry. The results of the present study reveal that high doses of bDLE increase the cell death in K562 and MOLT‑3 lines, without affecting the viability of human monocytes and murine peritoneal macrophages. Furthermore, low doses of bDLE induce differentiation in K562 cells towards a monocyte/macrophage lineage with an M2 phenotype, and induced moderately upregulated expression of CD42+, a megakaryocytic marker. Cell cycle arrest in the S and G2/M phases was observed in bDLE‑treated K562 cells, which demonstrated similar phagocytic activity, NO levels and cytokine and chemokine production to that of PMA‑treated cells. The present study demonstrates that bDLE exhibits an antileukemia effect, suggesting that it may be an effective candidate for leukemia treatment.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effect of bovine dialyzable leukocyte extract on induction of cell differentiation and death in K562 human chronic myelogenous leukemia cells

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