Open Access

Synergistic inhibitory effects of low‑dose decitabine in combination with bortezomib in the AML cell line Kasumi‑1

  • Authors:
    • Vassiliki Mpakou
    • Aris Spathis
    • Anthi Bouhla
    • Efthimia Mpazani
    • Sotirios Papageorgiou
    • Konstantinos Gkontopoulos
    • Eirini Glezou
    • Thomas Thomopoulos
    • Periklis Foukas
    • Vasiliki Pappa
  • View Affiliations

  • Published online on: January 8, 2021     https://doi.org/10.3892/etm.2021.9628
  • Article Number: 195
  • Copyright: © Mpakou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, the ability of the proteasome inhibitor bortezomib (BZ), an oxidative stress‑inducing agent, to sensitize acute myeloid leukemia (AML) cells to decitabine (Dacogen®, DAC; a DNA methyltransferase inhibitor), in terms of cell viability and differentiation, was investigated. Kasumi‑1 AML (M2) cells were treated with low‑dose DAC (10, 50, 100, 200 or 400 nΜ), with or without BZ (10 nM). Apoptosis and the cell cycle were evaluated after 24 h of treatment through fluorescence‑assisted cell sorting (FACS) with Annexin V/propidium iodide and DAPI staining, respectively. The expression levels of CD193, CD11b, CD13, CD14, CD15, CD16 and CD117 surface differentiation markers were evaluated by FACS after 6 days of treatment. The results indicated significant alterations in cell death and cell cycle phases in Kasumi‑1 cells following DAC and BZ combination treatment compared to untreated cells and cells with single treatments. Low‑dose DAC/BZ combinations significantly enhanced apoptosis and decreased the population of live Kasumi‑1 cells, with 100 and 200 nM of DAC and 10 nM BZ appearing to have the most potent synergistic effect according to a combination index. Furthermore, cell cycle profiling revealed that DAC/BZ treatment synergistically led to G0/G1‑ and G2/M‑phase arrest. By contrast, DAC appeared to promote monocytic and granulocytic differentiation of Kasumi‑1 cells more effectively alone than in combination with BZ. BZ acted synergistically with low‑dose DAC in vitro, leading to enhanced apoptosis and G0/G1‑ and G2/M‑phase arrest in AML cells, hence prohibiting either DNA synthesis or mitosis. Although further in vivo investigation is necessary, these results provide a strong rationale for the implementation of a combination treatment with DAC and bortezomib in AML therapy, followed by DAC alone, which may achieve better clinical responses and possibly partially overcome the frequently encountered DAC resistance of patients with AML.
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March-2021
Volume 21 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Mpakou V, Spathis A, Bouhla A, Mpazani E, Papageorgiou S, Gkontopoulos K, Glezou E, Thomopoulos T, Foukas P, Pappa V, Pappa V, et al: Synergistic inhibitory effects of low‑dose decitabine in combination with bortezomib in the AML cell line Kasumi‑1. Exp Ther Med 21: 195, 2021
APA
Mpakou, V., Spathis, A., Bouhla, A., Mpazani, E., Papageorgiou, S., Gkontopoulos, K. ... Pappa, V. (2021). Synergistic inhibitory effects of low‑dose decitabine in combination with bortezomib in the AML cell line Kasumi‑1. Experimental and Therapeutic Medicine, 21, 195. https://doi.org/10.3892/etm.2021.9628
MLA
Mpakou, V., Spathis, A., Bouhla, A., Mpazani, E., Papageorgiou, S., Gkontopoulos, K., Glezou, E., Thomopoulos, T., Foukas, P., Pappa, V."Synergistic inhibitory effects of low‑dose decitabine in combination with bortezomib in the AML cell line Kasumi‑1". Experimental and Therapeutic Medicine 21.3 (2021): 195.
Chicago
Mpakou, V., Spathis, A., Bouhla, A., Mpazani, E., Papageorgiou, S., Gkontopoulos, K., Glezou, E., Thomopoulos, T., Foukas, P., Pappa, V."Synergistic inhibitory effects of low‑dose decitabine in combination with bortezomib in the AML cell line Kasumi‑1". Experimental and Therapeutic Medicine 21, no. 3 (2021): 195. https://doi.org/10.3892/etm.2021.9628