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Remimazolan inhibits glioma cell growth and induces apoptosis through down-regulation of NF-κB pathway.
- Source :
-
IUBMB life [IUBMB Life] 2021 Feb; Vol. 73 (2), pp. 341-348. Date of Electronic Publication: 2020 Dec 24. - Publication Year :
- 2021
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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.<br /> (© 2020 International Union of Biochemistry and Molecular Biology.)
- Subjects :
- Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Cycle
Cell Movement
Down-Regulation
Glioma metabolism
Glioma pathology
Humans
NF-kappa B genetics
NF-kappa B metabolism
Tumor Cells, Cultured
Apoptosis
Benzodiazepines pharmacology
Brain Neoplasms drug therapy
Cell Proliferation
Gene Expression Regulation, Neoplastic drug effects
Glioma drug therapy
NF-kappa B antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1521-6551
- Volume :
- 73
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- IUBMB life
- Publication Type :
- Academic Journal
- Accession number :
- 33368968
- Full Text :
- https://doi.org/10.1002/iub.2433