Novel retinoic acid derivative induces differentiation and growth arrest in neuroblastoma
| Autor: | Elizabeth A. Beierle, Colin H. Quinn, Raoud Marayati, Adele P. Williams, Elizabeth Mroczek-Musulman, Laura V. Bownes, Venkatram R. Atigadda, Jerry E. Stewart |
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| Rok vydání: | 2020 |
| Předmět: |
Cell cycle checkpoint
Neurite Cell Survival Retinoic acid Tretinoin Naphthalenes Stem cell marker Article Mice Neuroblastoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Cell Line Tumor 030225 pediatrics medicine Animals Humans Cell Proliferation Cell growth business.industry Cell Differentiation General Medicine medicine.disease chemistry Cell culture 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health Fatty Acids Unsaturated Cancer research Surgery business |
| Zdroj: | J Pediatr Surg |
| ISSN: | 0022-3468 |
| Popis: | Introduction Retinoic acid (RA) is a differentiating agent utilized as maintenance therapy for high-risk neuroblastoma (NB), but associated toxicities limit its use. We have previously shown that a non-toxic, novel rexinoid, 9-cis-UAB30 (UAB30), decreased NB cell proliferation and in vivo tumor growth. A second generation, mono-methylated compound, 6-Methyl-UAB30 (6-Me), has been recently designed having greater potency compared with UAB30. In the current study, we hypothesized that 6-Me would inhibit NB cell proliferation and survival and induce differentiation and cell-cycle arrest. Methods Proliferation and viability were measured in four human NB cell lines following treatment with UAB30 or 6-Me. Cell-cycle was analyzed and tumor cell stemness was evaluated with extreme limiting dilution assays and immunoblotting for expression of stem cell markers. A xenograft murine model was utilized to study the effects of 6-Me in vivo. Results Treatment with 6-Me led to decreased proliferation and viability, induced cell cycle arrest, and increased neurite outgrowth, indicating differentiation of surviving cells. Furthermore, treatment with 6-Me decreased tumorsphere formation and expression of stem cell markers. Finally, inhibition of tumor growth and increased animal survival was observed in vivo following treatment with 6-Me. Conclusion These results indicate a potential therapeutic role for this novel rexinoid in neuroblastoma treatment. |
| Databáze: | OpenAIRE |
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