Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts.

Autor: Marayati R; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Bownes LV; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Quinn CH; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Wadhwani N; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Williams AP; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Markert HR; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Atigadda V; Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35233, USA., Aye JM; Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA., Stewart JE; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA., Yoon KJ; Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35233, USA., Beierle EA; Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, 1600 7th Ave. South, Lowder Building, Suite 300, Birmingham, AL 35233, USA. Electronic address: elizabeth.beierle@childrensal.org.
Jazyk: angličtina
Zdroj: Journal of pediatric surgery [J Pediatr Surg] 2021 Jun; Vol. 56 (6), pp. 1165-1173. Date of Electronic Publication: 2021 Feb 24.
DOI: 10.1016/j.jpedsurg.2021.02.041
Abstrakt: Introduction: The poor therapeutic efficacy seen with current treatments for neuroblastoma may be attributed to stem cell-like cancer cells (SCLCCs), a subpopulation of cancer cells associated with poor prognosis and disease recurrence. Retinoic acid (RA) is a differentiating agent used as maintenance therapy for high-risk neuroblastoma but nearly half of children treated with RA relapse. We hypothesized that 6-Methyl-UAB30 (6-Me), a second-generation rexinoid recently developed with a favorable toxicity profile compared to RA, would reduce cancer cell stemness in human neuroblastoma patient-derived xenografts (PDXs).
Methods: Cells from three neuroblastoma PDXs were treated with 6-Me and proliferation, viability, motility, and cell-cycle progression were assessed. CD133 expression, sphere formation, and mRNA abundance of stemness and differentiation markers were evaluated using flow cytometry, in vitro extreme limiting dilution analysis, and real-time PCR, respectively.
Results: Treatment with 6-Me decreased proliferation, viability, and motility, and induced cell-cycle arrest and differentiation in all three neuroblastoma PDXs. In addition, 6-Me treatment led to decreased CD133 expression, decreased sphere-forming ability, and decreased mRNA abundance of Oct4, Nanog, and Sox2, indicating decreased cancer cell stemness.
Conclusions: 6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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