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.

Basic information

Original name

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

Authors

MACSEK, Peter (703 Slovakia, belonging to the institution), Jan ŠKODA (203 Czech Republic, belonging to the institution), Mária KRCHNIAKOVÁ (703 Slovakia, belonging to the institution), Jakub NERADIL (203 Czech Republic, belonging to the institution) and Renata VESELSKÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14310/22:00125165

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/ijms23010376

UT WoS

000752216100001

Keywords in English

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

Abstract

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.

Links

NV16-34083A, research and development project

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

NV17-33104A, research and development project

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

Citovat

MACSEK, Peter, Jan ŠKODA, Mária KRCHNIAKOVÁ, Jakub NERADIL and Renata VESELSKÁ. Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma. 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.

@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.

Detailed Information on Publication Record