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@article{1820279, author = {Macsek, Peter and Škoda, Jan and Krchniaková, Mária and Neradil, Jakub and Veselská, Renata}, article_location = {Basel}, article_number = {1}, doi = {http://dx.doi.org/10.3390/ijms23010376}, keywords = {thiosemicarbazone; DpC; neuroblastoma; MYC; EGFR; NDRG1; lipid droplet}, language = {eng}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, title = {Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma}, url = {https://www.mdpi.com/1422-0067/23/1/376}, volume = {23}, year = {2022} }
TY - JOUR ID - 1820279 AU - Macsek, Peter - Škoda, Jan - Krchniaková, Mária - Neradil, Jakub - Veselská, Renata PY - 2022 TI - Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma JF - International Journal of Molecular Sciences VL - 23 IS - 1 SP - 376 EP - 376 PB - MDPI SN - 14220067 KW - thiosemicarbazone KW - DpC KW - neuroblastoma KW - MYC KW - EGFR KW - NDRG1 KW - lipid droplet UR - https://www.mdpi.com/1422-0067/23/1/376 N2 - 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. ER -
MACSEK, Peter, Jan ŠKODA, Mária KRCHNIAKOVÁ, Jakub NERADIL and Renata VESELSKÁ. Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2022, vol.~23, No~1, p.~376-393. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms23010376.
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