Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. CDDO-TEFEA is used to inhibit proliferation and induce apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM. This study evaluated the effects of CDDO-TFEA on GBM cells. To do this, we treated GBM8401 cell lines with CDDO-TFEA and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. CDDO-TFEA significantly inhibited the cell viability and induced cell apoptosis on GBM 8401 cell line. The annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with CDDO-TFEA led to a significant reduction in the GBM8401 cells' mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, treatment with CDDO-TFEA led to an accumulation of G/M-phase cells. In addition, these results suggest that regarding increased protein synthesis during mitosis in the MPM-2 staining, indicative of a delay in the G2 checkpoint. An analysis of Cyclin B1, CDK1, Cyclin B1/CDK1 complex and CHK1 and CHK2 expression suggested that cell cycle progression seems also to be regulated by CDDO-TFEA. Therefore, CDDO-TFEA may not only induce cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells. CDDO-TFEA can inhibit proliferation, cell cycle progression and induce apoptosis in GBM cells , possibly though its inhibition of Cyclin B1, CDK1 expression, and Cyclin B1/CDK1 association and the promotion of CHK1 and CHK2 expression.