14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death.
Cancer Gene Ther
; 21(4): 158-63, 2014 Apr.
Article
in En
| MEDLINE
| ID: mdl-24626062
ABSTRACT
14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
14-3-3 Proteins
Limits:
Humans
Language:
En
Journal:
Cancer Gene Ther
Year:
2014
Document type:
Article