remimazolam and Glioma

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.

Topics: Apoptosis; Benzodiazepines; Brain Neoplasms; Cell Cycle; Cell Movement; Cell Proliferation; Down-Regulation; Gene Expression Regulation, Neoplastic; Glioma; Humans; NF-kappa B; Tumor Cells, Cultured