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Research ArticleExperimental Studies

Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation

KAZUKI OTSUKA, MANABU SASADA, YU HIRANO, YUSUKE NOHARA, TAKUYA IYODA, YOSHIKAZU HIGAMI, HIROAKI KODAMA and FUMIO FUKAI
Anticancer Research July 2019, 39 (7) 3487-3492; DOI: https://doi.org/10.21873/anticanres.13494
KAZUKI OTSUKA
1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
2Department of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
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MANABU SASADA
1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
3Translational Research Center, Research Institutes for Science and Technology, Tokyo University of Science, Noda, Japan
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YU HIRANO
1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
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YUSUKE NOHARA
1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
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TAKUYA IYODA
4Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Japan
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YOSHIKAZU HIGAMI
2Department of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
3Translational Research Center, Research Institutes for Science and Technology, Tokyo University of Science, Noda, Japan
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HIROAKI KODAMA
5Department of Biochemistry, Faculty of Science and Engineering, Saga University, Saga, Japan
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FUMIO FUKAI
1Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
3Translational Research Center, Research Institutes for Science and Technology, Tokyo University of Science, Noda, Japan
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  • For correspondence: fukai{at}rs.noda.tus.ac.jp
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    Figure 1.

    Effects of ACR, ATRA, and TNIIIA2 on cell survival/proliferation. (A and B) IMR-32 cells were cultured as indicated for 6 days. (A) The number of viable cells was evaluated by the WST assay as described in the Materials and Methods. (B) Cell viablity was evaluated by Trypan blue exclusion test and the percentages of cells positive to Trypan blue to total cells are shown: data are shown as the means±SD (n=3). Statistical analysis was performed by non-parametric ANOVA and post hoc testing. **p<0.01; n.s.: Not significant.

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    Figure 2.

    Proteasomal degradation of N-Myc protein induced by a combination of ACR and TNIIIA2. IMR-32 cells were cultured as indicated for 6 days before western blotting analysis. (A) Detection of N-Myc and Aurora A. (B) Detection of N-Myc. At day 5, MG-132 was added to the cultured media.

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    Figure 3.

    Suppression of anchorage-independent growth by the ACR-TNIIIA2 combination. IMR-32 cells were cultured as indicated for 6 days and a soft agar formation assay was performed as described in the Materials and Methods. The results show the total amount of counts in 5 fields of each well at 4 weeks; data are shown as means±SD (n=3). Statistical analysis was performed by non-parametric ANOVA and post hoc testing. **p<0.01.

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    Figure 4.

    Combined administration of ACR and TNIIIA2 suppressed tumor growth in xenograft model mice. (A-C) Preparations of neuroblastoma xenograft model and chemotherapy with vehicle, ACR or the ACR-TNIIIA2 combination were performed as described in the Materials and Methods. (A) Relative tumor volume of each group in chemotherapy; data are shown as the means±SD (n=3). Statistical analysis was performed by Mann-Whitney U-test. *p<0.05; n.s.: Not significant. (B) Monitoring of body weight. (C) Western blotting analysis of N-Myc in tumor tissues on day 24.

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July 2019
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Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation
KAZUKI OTSUKA, MANABU SASADA, YU HIRANO, YUSUKE NOHARA, TAKUYA IYODA, YOSHIKAZU HIGAMI, HIROAKI KODAMA, FUMIO FUKAI
Anticancer Research Jul 2019, 39 (7) 3487-3492; DOI: 10.21873/anticanres.13494

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Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation
KAZUKI OTSUKA, MANABU SASADA, YU HIRANO, YUSUKE NOHARA, TAKUYA IYODA, YOSHIKAZU HIGAMI, HIROAKI KODAMA, FUMIO FUKAI
Anticancer Research Jul 2019, 39 (7) 3487-3492; DOI: 10.21873/anticanres.13494
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Keywords

  • Neuroblastoma
  • proto-oncogene
  • MYCN
  • N-Myc
  • retinoic acid
  • all-trans retinoic acid
  • Acyclic retinoid
  • Tenascin-C
  • integrin
  • ubiquitin-proteasome system
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