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. The anti-proliferative and anti-cancer activities of ROSC 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 having role in the regulation of glycogen synthase. It also has a role in multiple cellular processes as well as disease conditions. A member of the GSK3 family, GSK3β, has been implicated in many human malignancies including neuroblastoma. The specific inhibition of GSK3β was responsible for reducing neuroendocrine markers and suppressing neuroblastoma (NB) cell growth. NB is a malign pediatric disease with diverse types of tumors and high heterogeneity. Lately, GSK3β targeted therapy models are being investigated for NB therapy. The action of ROSC on GSK3β, however, is not fully understood. In this study, we showed that ROSC exerts anti-proliferative and apoptotic activity in SK-N-AS neuroblastoma cells by increasing reactive oxygen species (ROS) generation, which can be prevented by N-acetyl-cysteine administration. ROSC treatment inhibited GSK3β signaling by promoting Ser9 inhibitory phosphorylation. Together, ROSC at low doses can be a drug candidate to modulate GSK3β signaling in NB cells.

Keywords

• Neuroblastoma
• roscovitine
• cell cycle
• apoptosis
• GSK3β

References

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