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

J 2022

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

MACSEK, Peter; Jan ŠKODA; Mária KRCHNIAKOVÁ; Jakub NERADIL; Renata VESELSKÁ et al.

Základní údaje

Originální název

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

Autoři

MACSEK, Peter; Jan ŠKODA; Mária KRCHNIAKOVÁ; Jakub NERADIL a Renata VESELSKÁ

Vydání

International Journal of Molecular Sciences, Basel, MDPI, 2022, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/22:00125165

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

thiosemicarbazone; DpC; neuroblastoma; MYC; EGFR; NDRG1; lipid droplet

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 4. 2023 08:07, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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.

Návaznosti

NV16-34083A, projekt VaV

Název: Receptorové tyrozinkinázy a navazující signální dráhy jako potenciální cíle léčby refrakterních solidních nádorů dětského věku

NV17-33104A, projekt VaV

Název: Terapeutický potenciál nových thiosemicarbazonů v dětské onkologii: možnosti překonání Pgp-zprostředkované lékové rezistence

Citovat

MACSEK, Peter; Jan ŠKODA; Mária KRCHNIAKOVÁ; Jakub NERADIL a Renata VESELSKÁ. Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma. International Journal of Molecular Sciences. Basel: MDPI, 2022, roč. 23, č. 1, s. 376-393. ISSN 1422-0067. Dostupné z: https://doi.org/10.3390/ijms23010376.

@article{1820279,
   author = {Macsek, Peter and Škoda, Jan and Krchniaková, Mária and Neradil, Jakub and Veselská, Renata},
   article_location = {Basel},
   article_number = {1},
   doi = {https://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 a Renata VESELSKÁ. Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2022, roč.~23, č.~1, s.~376-393. ISSN~1422-0067. Dostupné z: https://doi.org/10.3390/ijms23010376.

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