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.
We are grateful to İstanbul Kultur University and İstanbul Medeniyet University, Science and Advanced Technologies Research Center (IMU-BILTAM) where the research was conducted.
Birincil Dil | İngilizce |
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Konular | Çocuk Hematolojisi ve Onkolojisi, Çocuk Nörolojisi, Kanser Hücre Biyolojisi |
Bölüm | Research Article |
Yazarlar | |
Yayımlanma Tarihi | 3 Ocak 2024 |
Gönderilme Tarihi | 26 Temmuz 2023 |
Kabul Tarihi | 10 Ekim 2023 |
Yayımlandığı Sayı | Yıl 2023 Cilt: 40 Sayı: 4 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.