Specific Inhibition of GSK-3β by Tideglusib: Potential Therapeutic Target for Neuroblastoma Cancer Stem Cells

Abstract

Neuroblastoma is an embryonic tumor that represents the most common extracranial solid tumor in children. Resistance to therapy is attributed, in part, to the persistence of a subpopulation of slowly dividing cancer stem cells (CSCs) within those tumors. Glycogen synthase kinase (GSK)-3β is an active proline-directed serine/threonine kinase, well-known to be involved in different signaling pathways entangled in the pathophysiology of neuroblastoma. This study aims to assess the potency of an irreversible GSK-3β inhibitor drug, Tideglusib (TDG), in suppressing proliferation, viability, and migration of human neuroblastoma cell lines, as well as its effects on their CSCs subpopulation in vitro and in vivo. Our results showed that treatment with TDG significantly reduced cell proliferation, viability, and migration of SK-N-SH and SH-SY5Y cells. TDG also significantly inhibited neurospheres formation capability in both cell lines, eradicating the self-renewal ability of highly resistant CSCs. Importantly, TDG potently inhibited neuroblastoma tumor growth and progression in vivo. In conclusion, TDG proved to be an effective in vitro and in vivo treatment for neuroblastoma cell lines and may hence serve as a potential adjuvant therapeutic agent for this aggressive nervous system tumor.

Tideglusib enhances odontogenic differentiation in human dental pulp stem cellsin vitro

“…cell types. Previous reports demonstrated that Tideglusib impaired the proliferation and migration of human neuroblastoma cell lines (Bahmad et al, 2020(Bahmad et al, , 2021 and human osteosarcoma cell lines (Wei et al, 2021). Thus, it can be speculated that the effect of Wnt on cell proliferation is cell type specific.…”

The Anticipated Effect of Glycogen Synthase kinase 3 (GSK3) Antagonist on Pulp Tissue Repair in Rabbits

“…Recent studies of the involvement of the GSK-3 in many diseases pathways leading to emerge it in the The Anticipated Effect of Glycogen Synthase Kinase 3 (GSK3) Antagonist on Pulp Tissue Repair (627) pharmacological chemistry research field as a very interesting therapeutic target for the development of selective inhibitors as potential new drugs (24,(26)(27)(28)(29) . So glycogen synthase kinases 3 (GSK3) inhibitors drug have been developed.…”