Preclinical assessment of JNJ-26854165 (Serdemetan), a novel tryptamine compound with radiosensitizing activity in vitro and in tumor xenografts.

Détails

ID Serval
serval:BIB_CC55BE91B23B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Preclinical assessment of JNJ-26854165 (Serdemetan), a novel tryptamine compound with radiosensitizing activity in vitro and in tumor xenografts.
Périodique
Cancer Letters
Auteur(s)
Chargari C., Leteur C., Angevin E., Bashir T., Schoentjes B., Arts J., Janicot M., Bourhis J., Deutsch E.
ISSN
1872-7980 (Electronic)
ISSN-L
0304-3835
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
312
Numéro
2
Pages
209-218
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Serdemetan (JNJ-26854165) is a novel tryptamine compound with antiproliferative activity in various p53 wild-type (WT) tumor cell lines. We investigated its potential as radiosensitizer using four human cancer cell lines: H460, A549, p53-WT-HCT116, and p53-null-HCT116. Serdemetan inhibited clonogenic survival in all cell lines, but in a lower extent in p53-null-HCT116. In the combination studies, Serdemetan treatment at 0.25μM in H460 and at 5μM in A549 cells resulted in a sensitivity-enhancement ratio of 1.18 and 1.36, respectively. At 2Gy, surviving fractions were 0.72 and 0.97 for p53-WT HCT116 and p53-null cells exposed to 0.5μM of Serdemetan, respectively (p<0.05). Radiosensitization of H460 and A549 cells was associated with G2/M cell cycle arrest and with an increased expression of p53 and p21. In vivo, Serdemetan caused a greater than additive increase in tumor growth delay. The dose enhancement factor was 1.9 and 1.6 for H460 and A549 tumors, respectively. Serdemetan inhibited proliferation, capillary tube formation and migration of HMEC-1 cells. These effects were more marked concurrently with irradiation. These results in tumor and endothelial cells suggest that Serdemetan has potential as a radiosensitizer. Further investigations are warranted with regard to the molecular mechanisms underlying its actions and its dependency regarding p53 status.
Mots-clé
Blotting, Western, Cell Cycle, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Drug Evaluation, Preclinical, Humans, Radiation-Sensitizing Agents/pharmacology, Tryptamines/pharmacology, Tumor Suppressor Protein p53/metabolism, Xenograft Model Antitumor Assays
Pubmed
Web of science
Création de la notice
01/12/2014 17:41
Dernière modification de la notice
20/08/2019 16:47
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