Ghent University Academic Bibliography

Advanced

The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors

Deborah Castelletti, Giulio Fiaschetti, Valeria Di Dato, Urs Ziegler, Candy Kumps, Katleen De Preter UGent, Massimo Zollo, Franki Speleman UGent, Tarek Shalaby, Daniela De Martino, et al. (2010) MOLECULAR CANCER THERAPEUTICS. 9(12). p.3145-3157
abstract
The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G(1)/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
C-MYC, CENTRAL-NERVOUS-SYSTEM, ONCOGENE EXPRESSION, NEUROBLASTOMA, PHOSPHORYLATION, CAP-DEPENDENT TRANSLATION, SURVIVAL, ANTITUMOR-ACTIVITY, MEDULLOBLASTOMA, ACTIVATION
journal title
MOLECULAR CANCER THERAPEUTICS
Mol.Cancer Ther.
volume
9
issue
12
pages
3145 - 3157
Web of Science type
Article
Web of Science id
000285296300005
JCR category
ONCOLOGY
JCR impact factor
5.225 (2010)
JCR rank
28/181 (2010)
JCR quartile
1 (2010)
ISSN
1535-7163
DOI
10.1158/1535-7163.MCT-10-0539
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1176758
handle
http://hdl.handle.net/1854/LU-1176758
date created
2011-02-28 16:29:16
date last changed
2016-12-19 15:45:51
@article{1176758,
  abstract     = {The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G(1)/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET.},
  author       = {Castelletti, Deborah and Fiaschetti, Giulio and Di Dato, Valeria and Ziegler, Urs and Kumps, Candy and De Preter, Katleen and Zollo, Massimo and Speleman, Franki and Shalaby, Tarek and De Martino, Daniela and Berg, Thorsten and Eggert, Angelika and Arcaro, Alexandre and Grotzer, Michael A},
  issn         = {1535-7163},
  journal      = {MOLECULAR CANCER THERAPEUTICS},
  keyword      = {C-MYC,CENTRAL-NERVOUS-SYSTEM,ONCOGENE EXPRESSION,NEUROBLASTOMA,PHOSPHORYLATION,CAP-DEPENDENT TRANSLATION,SURVIVAL,ANTITUMOR-ACTIVITY,MEDULLOBLASTOMA,ACTIVATION},
  language     = {eng},
  number       = {12},
  pages        = {3145--3157},
  title        = {The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors},
  url          = {http://dx.doi.org/10.1158/1535-7163.MCT-10-0539},
  volume       = {9},
  year         = {2010},
}

Chicago
Castelletti, Deborah, Giulio Fiaschetti, Valeria Di Dato, Urs Ziegler, Candy Kumps, Katleen De Preter, Massimo Zollo, et al. 2010. “The Quassinoid Derivative NBT-272 Targets Both the AKT and ERK Signaling Pathways in Embryonal Tumors.” Molecular Cancer Therapeutics 9 (12): 3145–3157.
APA
Castelletti, D., Fiaschetti, G., Di Dato, V., Ziegler, U., Kumps, C., De Preter, K., Zollo, M., et al. (2010). The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors. MOLECULAR CANCER THERAPEUTICS, 9(12), 3145–3157.
Vancouver
1.
Castelletti D, Fiaschetti G, Di Dato V, Ziegler U, Kumps C, De Preter K, et al. The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors. MOLECULAR CANCER THERAPEUTICS. 2010;9(12):3145–57.
MLA
Castelletti, Deborah, Giulio Fiaschetti, Valeria Di Dato, et al. “The Quassinoid Derivative NBT-272 Targets Both the AKT and ERK Signaling Pathways in Embryonal Tumors.” MOLECULAR CANCER THERAPEUTICS 9.12 (2010): 3145–3157. Print.