Mesenchymal Stem Cells Promote Caspase Expression in Molt-4 Leukemia Cells Via GSK-3α/Β and ERK1/2 Signaling Pathways as a Therapeutic Strategy

Abstract

Background: Mesenchymal stem cells (MSCs) are considered an interesting tool in cell therapy due to their unique features such as self-renewal, multi-potency, and pluripotency. The multifunctional properties of these cells are being investigated in many studies. The current research examined the influence of MSCs on the Molt-4 cell line as acute lymphoblastic leukemia (ALL) cells.

Methods: MSCs were cultured, characterized, and co-cultured with Molt-4 cells in a trans-well system. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to western blotting for protein expression assessment. Telomerase activity as well as cell senescence, were investigated by PCR-ELISA TRAP assay and β-galactosidase activity measurement, respectively.

Results: It was found that MSCs resulted in a significant increase in the pro-caspase-8 and cleaved-caspase 8 and 9 expression levels. Furthermore, protein expression levels of GSK-3α/β and ERK1/2 were significantly decreased. The results also showed that MSCs caused significant decreases and increases in telomerase and β-galactosidase enzyme activity of Molt-4 cells, respectively.

Conclusion: It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis and cell senescence via caspase-8, 9 cascade and GSK-3α/β and ERK1/2 signaling pathways.

Keywords: GSK-3α/β and ERK1/2 signaling pathways; Mesenchymal stem cells; apoptosis; caspase 8 and 9; stem cell-based therapy.