Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation.
Animals
Antineoplastic Agents
/ pharmacology
Cell Proliferation
/ drug effects
Mice, Inbred BALB C
Mice, Nude
N-Myc Proto-Oncogene Protein
/ metabolism
Neuroblastoma
/ drug therapy
Peptides
/ pharmacology
Phenotype
Tenascin
/ pharmacology
Tretinoin
/ analogs & derivatives
Tumor Burden
/ drug effects
MYCN
N-Myc
Neuroblastoma
acyclic retinoid
all-trans retinoic acid
integrin
proto-oncogene
retinoic acid
tenascin-C
ubiquitin-proteasome system
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
06
05
2019
revised:
01
06
2019
accepted:
03
06
2019
entrez:
3
7
2019
pubmed:
3
7
2019
medline:
10
7
2019
Statut:
ppublish
Résumé
Despite intensive chemotherapy, the survival rates for high-risk neuroblastoma, most of which have MYCN amplification, remain low. Overexpression of N-myc oncoprotein promotes expression of cancer-associated properties. We recently found that combination of all-trans retinoic acid (ATRA) with the β1-integrin-activating peptide TNIIIA2 attenuated cancer-associated properties of neuroblastoma cells through N-Myc degradation. However, ATRA has serious side-effects and there are concerns about late adverse effects. The aim of this study was to examine the effects of the combination of acyclic retinoid (ACR) with TNIIIA2 on neuroblastoma. The effects of ACR and TNIIIA2 were examined by neuroblastoma cell proliferation and survival assays as well as by using a neuroblastoma xenograft model. The levels of N-Myc and cancer-associated malignant properties were assayed by western blot and colony formation assay, respectively. Combining ACR, which is clinically safe, with TNIIIA2 induced proteasomal degradation of N-Myc and reduction of neuroblastoma cell malignant properties. An in vivo experiment showed therapeutic potential. ACR-TNIIIA2 combination treatment may be efficacious and clinical safe chemotherapy for high-risk neuroblastoma.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Despite intensive chemotherapy, the survival rates for high-risk neuroblastoma, most of which have MYCN amplification, remain low. Overexpression of N-myc oncoprotein promotes expression of cancer-associated properties. We recently found that combination of all-trans retinoic acid (ATRA) with the β1-integrin-activating peptide TNIIIA2 attenuated cancer-associated properties of neuroblastoma cells through N-Myc degradation. However, ATRA has serious side-effects and there are concerns about late adverse effects. The aim of this study was to examine the effects of the combination of acyclic retinoid (ACR) with TNIIIA2 on neuroblastoma.
MATERIALS AND METHODS
METHODS
The effects of ACR and TNIIIA2 were examined by neuroblastoma cell proliferation and survival assays as well as by using a neuroblastoma xenograft model. The levels of N-Myc and cancer-associated malignant properties were assayed by western blot and colony formation assay, respectively.
RESULTS
RESULTS
Combining ACR, which is clinically safe, with TNIIIA2 induced proteasomal degradation of N-Myc and reduction of neuroblastoma cell malignant properties. An in vivo experiment showed therapeutic potential.
CONCLUSION
CONCLUSIONS
ACR-TNIIIA2 combination treatment may be efficacious and clinical safe chemotherapy for high-risk neuroblastoma.
Identifiants
pubmed: 31262872
pii: 39/7/3487
doi: 10.21873/anticanres.13494
doi:
Substances chimiques
Antineoplastic Agents
0
N-Myc Proto-Oncogene Protein
0
Peptides
0
Tenascin
0
Tretinoin
5688UTC01R
3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
81485-25-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3487-3492Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.