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

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MACSEK Peter ŠKODA Jan KRCHNIAKOVÁ Mária NERADIL Jakub VESELSKÁ Renata

Rok publikování 2022
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Molecular Sciences
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.mdpi.com/1422-0067/23/1/376
Doi http://dx.doi.org/10.3390/ijms23010376
Klíčová slova thiosemicarbazone; DpC; neuroblastoma; MYC; EGFR; NDRG1; lipid droplet
Popis 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 MYCN 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 MYCN-amplified and c-MYC in MYCN-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.
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