Autophagy Promotes Survival of CHP-212 Neuroblastoma Cells Treated With Casiopeínas®

Anticancer Res. 2019 Jul;39(7):3687-3695. doi: 10.21873/anticanres.13517.

Abstract

Background: Neuroblastoma is the main solid extracranial tumor of childhood. The amplification of N-myc oncogene (MYCN) and 1p deletion are the main molecular alterations. These features are what make treatment impossible, especially in high-risk patients with metastases.

Materials and methods: Our study investigated the processes undergone by CHP-212 neuroblastoma cells, after being treated with Casiopeínas® (Cas) IIgly, IIIEa, and IIIia for 2, 10, and 24 h.

Results: At 2 h, all the treatments Ied to apoptosis [defined by the presence of B-cell lymphoma 2 (BCL2), BCL2-associated X protein, cytochrome c, and caspase-3]. In addition, autophagy with specific molecules beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I (ratio >1). Later at 10 h, autophagy-associated proteins were observed, and at 24 h, only survival proteins nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), and extracellular signal-regulated kinases (ERK)2/ERK1>1 were found. Another relevant finding was the presence of caspase-10 throughout the study, especially in cells treated with CasIIgly and CasIIIEa.

Conclusion: These relationships indicate a possible mechanism of action of Casiopeínas on neuroblastoma.

Keywords: Casiopeínas®; Neuroblastoma cells CHP-212; autophagy; caspase-10; survival.

MeSH terms

  • Autophagy / drug effects
  • Beclin-1 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / pharmacology*
  • Cytochromes c / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism*
  • Phenanthrolines / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • (Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)(H2O))NO3
  • BCL2 protein, human
  • Beclin-1
  • Coordination Complexes
  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • Phenanthrolines
  • Proto-Oncogene Proteins c-bcl-2
  • Cytochromes c
  • Extracellular Signal-Regulated MAP Kinases