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Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3ß.
Bahmad, Hisham F; Chalhoub, Reda M; Harati, Hayat; Bou-Gharios, Jolie; Assi, Sahar; Ballout, Farah; Monzer, Alissar; Msheik, Hiba; Araji, Tarek; Elajami, Mohamad K; Ghanem, Paola; Chamaa, Farah; Kadara, Humam; Abou-Antoun, Tamara; Daoud, Georges; Fares, Youssef; Abou-Kheir, Wassim.
Afiliación
  • Bahmad HF; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Chalhoub RM; Neuroscience Research Center, Faculty of Medicine, Lebanese University, Beirut, Lebanon.
  • Harati H; Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL, USA.
  • Bou-Gharios J; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Assi S; Medical Scientist Training Program, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
  • Ballout F; Neuroscience Research Center, Faculty of Medicine, Lebanese University, Beirut, Lebanon.
  • Monzer A; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Msheik H; Neuroscience Research Center, Faculty of Medicine, Lebanese University, Beirut, Lebanon.
  • Araji T; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Elajami MK; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Ghanem P; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Chamaa F; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Kadara H; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Abou-Antoun T; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Daoud G; Department of Internal Medicine, Mount Sinai Medical Center, Miami Beach, FL, USA.
  • Fares Y; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
  • Abou-Kheir W; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Pharmacol Rep ; 73(1): 211-226, 2021 Feb.
Article en En | MEDLINE | ID: mdl-33030673
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)-3ß is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3ß 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-3ß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiadiazoles / Células Madre Neoplásicas / Neoplasias Encefálicas / Glucógeno Sintasa Quinasa 3 beta / Neuroblastoma / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Pharmacol Rep Asunto de la revista: FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Líbano Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiadiazoles / Células Madre Neoplásicas / Neoplasias Encefálicas / Glucógeno Sintasa Quinasa 3 beta / Neuroblastoma / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Pharmacol Rep Asunto de la revista: FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Líbano Pais de publicación: Suiza