<em>In vitro</em> assessment of the efficiency of the PIM‑1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma

Alsubaie,Mona; Matou‑Nasri,Sabine; Aljedai,Abdullah; Alaskar,Ahmed; Al‑Eidi,Hamad; Albabtain,Sarah A.; Aldilaijan,Khawlah E.; Alsayegh,Manal; Alabdulkareem,Ibrahim B.

doi:10.3892/ol.2021.12883

In vitro assessment of the efficiency of the PIM‑1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma

Authors:
- Mona Alsubaie
- Sabine Matou‑Nasri
- Abdullah Aljedai
- Ahmed Alaskar
- Hamad Al‑Eidi
- Sarah A. Albabtain
- Khawlah E. Aldilaijan
- Manal Alsayegh
- Ibrahim B. Alabdulkareem
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Affiliations: Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard‑Health Affairs, Riyadh 11481, Saudi Arabia, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia, Research Department, Health Sciences Research Center, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia
Published online on: June 29, 2021 https://doi.org/10.3892/ol.2021.12883
Article Number: 622
Copyright: © Alsubaie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Burkitt's lymphoma is an aggressive form of lymphoma affecting B lymphocytes. It occurs endemically in Africa and sporadically in the rest of the world. Due to the high proliferation rate of this tumor, intensive multi‑drug treatment is required; however, the risk of tumor syndrome lysis is high. Overexpression of the proto‑oncogene proviral integration of the Moloney murine leukemia virus (PIM‑1) kinase is associated with the development of hematological abnormalities, including Burkitt's lymphoma (BL). PIM‑1 primarily exerts anti‑apoptotic activities through BAD phosphorylation. The aim of the present study was to investigate the in vitro efficiency of a PIM‑1 kinase pharmacological inhibitor (PIM1‑1) in BL. The impact of PIM1‑1 was evaluated in terms of the viability and apoptosis status of the BL B cell lines, Raji and Daudi, compared with K562 leukemia cells, which highly express PIM‑1. Cell viability and apoptotic status were assessed with western blotting, and PIM‑1 gene expression was assessed with reverse transcription‑quantitative PCR. After 48 h of treatment, PIM1‑1 inhibited the Daudi, Raji and K562 cell viability with a half‑maximal inhibitory concentration corresponding to 10, 20 and 30 µM PIM1‑1, respectively. A significant decrease of ERK phosphorylation was detected in PIM1‑1‑treated Daudi cells, confirming the antiproliferative effect. The addition of 10 µM PIM1‑1 significantly decreased the PIM‑1 protein and gene expression in Daudi cells. An inhibition of the pro‑apoptotic BAD phosphorylation was observed in the Daudi cells treated with 0.1‑1 µM PIM1‑1 and 10 µM PIM1‑1 decreased BAD phosphorylation in the Raji cells. The apoptotic status of both PIM1‑1‑treated cells lines were confirmed with the detection of cleaved capase‑3. However, no change in cell viability and PIM‑1 protein expression was observed in the 10 µM PIM1‑1‑treated K562 cells. In conclusion, the findings indicated that the PIM1‑1 pharmacological inhibitor may have therapeutic potential in BL, but with lower efficiency in leukemia.

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