Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targetin
- PDF / 6,721,620 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 54 Downloads / 142 Views
ARTICLE
Tideglusib attenuates growth of neuroblastoma cancer stem/ progenitor cells in vitro and in vivo by specifically targeting GSK‑3β Hisham F. Bahmad1,2,5 · Reda M. Chalhoub1,6 · Hayat Harati2 · Jolie Bou‑Gharios1,2 · Sahar Assi1 · Farah Ballout1 · Alissar Monzer1 · Hiba Msheik1 · Tarek Araji1 · Mohamad K. Elajami1,7 · Paola Ghanem1 · Farah Chamaa1 · Humam Kadara3 · Tamara Abou‑Antoun4 · Georges Daoud1 · Youssef Fares2 · Wassim Abou‑Kheir1 Received: 4 July 2020 / Revised: 1 September 2020 / Accepted: 19 September 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
Abstract Background Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor among the pediatric population. It is an embryonic tumor with high relapse rates pertaining to the presence of dormant slowly dividing cancer stem cells (CSC) within the tumor bulk that are responsible for therapy resistance. Therefore, there is a dire need to develop new therapeutic approaches that specifically target NB CSCs. Glycogen synthase kinase (GSK)-3β is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3β sustains the survival and maintenance of CSCs and renders them insensitive to chemotherapeutic agents and radiation. Methods In our study, we aimed at evaluating the potential anti-tumor effect of Tideglusib (TDG), an irreversible GSK-3β inhibitor drug, on three human NB cell lines, SK-N-SH, SH-SY5Y, and IMR-32. Results Our results showed that TDG significantly reduced cell proliferation, viability, and migration of the NB cells, in a dose- and time-dependent manner, and also significantly hindered the neurospheres formation eradicating the self-renewal ability of highly resistant CSCs. Besides, TDG potently reduced CD133 cancer stem cell marker expression in both SH-SY5Y cells and G1 spheres. Lastly, TDG inhibited NB tumor growth and progression in vivo. Conclusion Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role. Keywords Neuroblastoma · GSK-3β · Tideglusib · Cancer stem cells · Targeted therapy
Introduction
Hisham F. Bahmad, Reda M. Chalhoub and Hayat Harati have contributed equally to this work as co-first authors. Georges Daoud, Youssef Fares and Wassim Abou-Kheir have contributed equally to this work as joint senior authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43440-020-00162-7) contains supplementary material, which is available to authorized users. * Georges Daoud [email protected] * Youssef Fares [email protected] Extended author information available on the last page of the article
Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor in the pediatric population [1]. It accounts for around 15% o
Data Loading...
