COX-2 Acts as a Key Mediator of Trifluoperazine-induced Cell Death in U87MG Glioma Cells.

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is one of the most common brain tumors with a poor prognosis. Previously, we reported that trifluoperazine (TFP), a well-known antipsychotic, has anti-glioma activity through the modulation of intracellular calcium levels. The present study aimed to investigate the anti-cancer mechanism of action of TFP on glioma cells.

MATERIALS AND

METHODS

The effect of TFP on U87MG cells was examined using a viability assay, flow cytometry, enzyme-linked immunosorbent assay, quantitative real-time PCR, western blot analysis, colony formation, and immunocytochemistry.

RESULTS

TFP treatment decreased cell viability. To test the possible involvement of COX-2 in the anticancer activity of TFP on U87MG cells, a COX-2 inhibitor was applied. COX-2 inhibitor pretreatment restored TFP-induced reduction in viability to the control level. Additionally, TFP-induced changes in the apoptotic cell population, production of prostaglandins (PGE2, PGD2, 15d-PGJ2), and nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ) were ameliorated by COX-2 inhibitor pretreatment.

CONCLUSION

TFP suppressed the proliferation of U87MG glioma cell in a COX-2/PPARγ-dependent manner.