Roscovitine inhibits glycogen synthase kinase 3 beta signaling and exerts apoptotic effect with an increase in reactive oxygen species generation in neuroblastoma cells

Abstract

Roscovitine (ROSC) is a selective cyclin-dependent kinase (CDK) inhibitor against CDK2, 7 and 9. ROSC's anti-proliferative and anti-cancer activities have been well-documented in both in vivo and in vitro studies against several cancer types. Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase that has a role in the regulation of glycogen synthase. It also has a role in multiple cellular processes and disease conditions. A member of the GSK3 family, GSK3?, has been implicated in many human malignancies including neuroblastoma. The specific inhibition of GSK3? reduced neuroendocrine markers and suppressed neuroblastoma (NB) cell growth. NB is a malign pediatric disease with diverse types of tumors and high heterogeneity. Lately, GSK3? targeted therapy models are being investigated for NB therapy. The action of ROSC on GSK3?, however, is not fully understood. In this study, we showed that ROSC exerts anti-proliferative and apoptotic activity in SK-NAS neuroblastoma cells by increasing reactive oxygen species (ROS) generation, which can be prevented by N-acetyl-cysteine administration. ROSC treatment inhibited GSK3? signaling by promoting Ser9 inhibitory phosphorylation. ROSC at low doses can be a drug candidate to modulate GSK3? signaling in NB cells. © 2025 Elsevier B.V., All rights reserved.