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Biological evaluation of pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea derivatives as potential anti-angiogenetic agents in the treatment of neuroblastoma

Authors
  • Marengo, Barbara
  • Meta, Elda
  • Brullo, Chiara
  • De Ciucis, Chiara
  • Colla, Renata
  • Speciale, Andrea
  • Garbarino, Ombretta
  • Bruno, Olga
  • Domenicotti, Cinzia
Type
Published Article
Journal
Oncotarget
Publisher
"Impact Journals, LLC "
Publication Date
Sep 15, 2020
Volume
11
Issue
37
Pages
3459–3472
Identifiers
DOI: 10.18632/oncotarget.27733
PMID: 32973970
PMCID: PMC7500105
Source
PubMed Central
Keywords
License
Green

Abstract

Pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea compounds (STIRUR 13, STIRUR 41 and BUR 12) have been demonstrated to exert a strong inhibitory effect on interleukin 8 or N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis of human neutrophils. Since the migration of cancer cells is comparable to that of neutrophils, the purpose of this study is to evaluate the biological effect of STIRUR 13, STIRUR 41 and BUR 12 on ACN and HTLA-230, two neuroblastoma (NB) cell lines with different degree of malignancy. HTLA-230 cells, stage-IV NB cells, have high plasticity and can serve as progenitors of endothelial cells. The results herein reported show that the three tested compounds were not cytotoxic for both NB cells and did not alter their clonogenic potential. However, all compounds were able to inhibit the ability of HTLA-230 to form vascular-like structures. On the basis of these findings, pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea derivatives could be proposed as agents potentially effective in counteracting NB malignancy by inhibiting cell migration and tumor angiogenesis which represent important hallmarks responsible for cancer survival and progression.

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