RT Journal Article
T1 HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib small compound.
A1 Ramírez, Alberto
A1 Boulaiz, Houria
A1 Morata-Tarifa, Cynthia
A1 Perán, Macarena
A1 Jiménez, Gema
A1 Picon-Ruiz, Manuel
A1 Agil, Ahmad
A1 Cruz-López, Olga
A1 Conejo-García, Ana
A1 Campos, Joaquín M
A1 Sánchez, Ana
A1 García, María A
A1 Marchal, Juan A
K1 HER-2
K1 Bozepinib
K1 Protein kinases
K1 Cancer stem-like cells
K1 Metastasis
K1 Animales
K1 Carcinogénesis
K1 Neoplasias del colon
K1 Regulación hacia abajo
K1 Femenino
K1 Erizos
K1 Humanos
K1 Ratones desnudos
K1 Recurrencia local de neoplasia
K1 Células madre neoplásicas
K1 Oxazepinas
K1 Purinas
K1 Piranos
K1 Receptor ErbB-2
K1 Transducción de señal
K1 Regulación hacia arriba
K1 Factor A de crecimiento endotelial vascular
K1 beta Catenina
AB Identification of novel anticancer drugs presenting more than one molecular target and efficacy against cancer stem-like cells (CSCs) subpopulations represents a therapeutic need to combat the resistance and the high risk of relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine], a small anti-tumor compound, demonstrated selectivity on cancer cells and showed an inhibitory effect over kinases involved in carcinogenesis, proliferation and angiogenesis. The cytotoxic effects of Bozepinib were observed in both breast and colon cancer cells expressing different receptor patterns. Bozepinib inhibited HER-2 signaling pathway and JNK and ERKs kinases. In addition, Bozepinib has an inhibitory effect on AKT and VEGF together with anti-angiogenic and anti-migratory activities. Moreover, the modulation of pathways involved in tumorigenesis by Bozepinib was also evident in microarrays analysis. Interestingly, Bozepinib inhibited both mamo- and colono-spheres formation and eliminated ALDH+ CSCs subpopulations at a low micromolar range similar to Salinomycin. Bozepinib induced the down-regulation of c-MYC, β-CATENIN and SOX2 proteins and the up-regulation of the GLI-3 hedgehog-signaling repressor. Finally, Bozepinib shows in vivo anti-tumor and anti-metastatic efficacy in xenotransplanted nude mice without presenting sub-acute toxicity. These findings support further studies on the therapeutic potential of Bozepinib in cancer patients.
PB Impact Journals
YR 2014
FD 2014-06-15
LK http://hdl.handle.net/10668/2277
UL http://hdl.handle.net/10668/2277
LA en
NO Ramírez A, Boulaiz H, Morata-Tarifa C, Perán M, Jiménez G, Picon-Ruiz M, et al. HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib small compound. Oncotarget. 2014                         ; 5(11):3590-606
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 18, 2025