Stmc-03. repositioning chlorpromazine against chemoresistant glioma through the inhibition of cytochrome c oxidase

Chlorpromazine (CPZ) is an FDA-approved phenothiazine widely used as psychotropic in clinical practice. The pharmacological mechanism is through blockage of dopamine receptor. Recent reports have demonstrated some anti-proliferative activity against colon and brain tumors. However, the effect of CPZ in chemoresistant glioma has not yet been reported. Chemoresistant patient derived glioma stem cells and glioma cell lines were used to investigate the inhibitory mechanism of CPZ. CPZ effectively inhibited tumor growth and induced cell cycle arrest through the inhibition of cytochrome c oxidase subunit 4 isoform 1. Inhibition of cell growth by CPZ is reactive oxygen species- dependent through p38 MAP-kinase activation and down-regulation of the oncoprotein BMI, resulting in stem cell depletion. Moreover, in orthotopic mouse brain tumor models, CPZ treatment is associated with significant increase in the median overall survival. These data suggest that CPZ can be repositioned for treating chemoresistant glioma tumors.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research