Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma.

Peter Macsek, Jan Skoda, Maria Krchniakova, Jakub Neradil, Renata Veselska

Journal: International journal of molecular sciences 2022;23(1):

PMID: 35008802

Abstract

Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in -amplified and c-MYC in -nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.

DOI: 10.3390/ijms23010376

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Full Text Sources:

Medical:

https://medlineplus.gov/neuroblastoma.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-802

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-EGFR-8

MeSH Terms: Cell Cycle Proteins, Cell Line, Tumor, Cell Shape, Down-Regulation, ErbB Receptors, Gene Amplification, Gene Silencing, Humans, Intracellular Signaling Peptides and Proteins, Iron Chelating Agents, Models, Biological, N-Myc Proto-Oncogene Protein, Neuroblastoma, Phosphorylation, Proto-Oncogene Proteins c-akt, Pyridines, Signal Transduction, Stress, Physiological, Thiosemicarbazones, Up-Regulation