Virtual Conference
Pharma Conference 2022

Sabine Matou-Nasri

King Abdullah International Medical Research Center, Saudi Arabia

Title: An in vitro assessment of the efficiency of the PIM-1 kinase pharmacological inhibitor (PIM1-1) as a potential treatment for Burkitt’s lymphoma

Abstract

The overexpression of the proto-oncogene Proviral Integration of the Moloney virus (PIM-1) kinase is correlated with the development of hematological abnormalities, including Burkitt’s Lymphoma (BL). PIM-1 primarily exerts anti-apoptotic activities through BAD phosphorylation. The aim of this study was to investigate the in vitro efficiency of a PIM-1 kinase pharmacological inhibitor (PIM1-1) in BL. The impact of the PIM1-1 was evaluated in terms of the viability and apoptosis status of the BL B-cell lines, Raji and Daudi, compared to K562 leukemic cells, which highly express PIM-1. Cell viability and apoptotic status were assessed with Western blotting and the PIM-1 gene expression with RT-quantitative PCR. After 48 hours of treatment, the 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 the Extracellular Signal-regulated Kinase (ERK) phosphorylation was detected in the PIM1-1-treated Daudi cells, confirming the anti-proliferative 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 the PIM1-1-treated cells was confirmed with the detection of cleaved-capase-3. However, at the 10 µM PIM1-1 tested, no change in cell viability and PIM-1 protein expression was observed in the PIM1-1-treated K562 cells. In conclusion, the findings indicate that the PIM1-1 pharmacological inhibitor may have a substantial therapeutic potential in BL, but with lower efficiency in leukemia.

Biography

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