Remimazolan inhibits glioma cell growth and induces apoptosis through down‐regulation of NF‐κB pathway

Abstract Glioma alone accounts for 30% of various kinds of primary brain tumors and is the highest cause of mortality associated with intracranial malignant cancers. In the present study, Suzuki‐coupling products of remimazolan were synthesized and investigated for anti‐neoplastic property against glioma cells. RFMSP treatment for 48 hr suppressed viabilities of U‐118MG and U87MG cells in dose dependent manner. Exposure of primary astrocytes to RFMSP at 2–20 μM concentration range minimally affected viabilities. RFMSP treatment at 5 μM doses raised apoptotic cell count to 53.8 ± 2.3% and 48.2 ± 1.8%, respectively in U‐118MG and U87MG cells. Treatment of the cells with RFMSP induced nuclear condensation and subsequent fragmentation. In RFMSP treated U‐118MG and U87MG cells, NF‐κB p65 expression was markedly suppressed compared to the control cells. Additionally, RFMSP treatment decreased the ratio of nuclear to total NF‐κB p65 level in both the cell lines. Treatment of U‐118MG and U87MG cells with 5 μM RFMSP for 48 hr caused a marked down‐regulation in survivin and XIAP levels. Treatment with RFMSP promoted Bax expression and suppressed Bcl‐2 level. The caspase‐9 and ‐3 activation was markedly induced by RFMSP treatment in U‐118MG and U87MG cells compared to the control cells. In summary, the RFMSP synthesized by Suzuki‐coupling of RFMSP inhibited glioma cell survival via DNA damage mediated apoptosis. The anti‐glioma potential of RFMSP involved down‐regulation of NF‐κB expression, targeted survivin & XIAP levels and induced caspase activation in glioma cells. Therefore, RFMSP may be studied further as therapeutic agent for the treatment of glioma.