Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor and refractory to existing therapies. The oncogene BMI-1, a member of Polycomb Repressive Complex 1 (PRC1) plays essential roles in various human cancers and becomes an attractive therapeutic target. Here we showed that BMI-1 is highly expressed in GBM and especially enriched in glioblastoma stem cells (GSCs). Then we comprehensively investigated the anti-GBM effects of PTC-209, a novel specific inhibitor of BMI-1. We found that PTC-209 efficiently downregulates BMI-1 expression and the histone H2AK119ub1 levels at microM concentrations. In vitro, PTC-209 effectively inhibits glioblastoma cell proliferation and migration, and GSC self-renewal. Transcriptomic analyses of TCGA datasets of glioblastoma and PTC-209-treated GBM cells demonstrate that PTC-209 reverses the altered transcriptional program associated with BMI-1 overexpression. And Chromatin Immunoprecipitation assay confirms that the derepressed tumor suppressor genes belong to BMI-1 targets and the enrichment levels of H2AK119ub1 at their promoters is decreased upon PTC-209 treatment. Strikingly, the glioblastoma growth is significantly attenuated by PTC-209 in a murine orthotopic xenograft model. Therefore our study provides proof-of-concept for inhibitors targeting BMI-1 in potential applications as an anti-GBM therapy.
 ...
PMID:Targeting of BMI-1 with PTC-209 inhibits glioblastoma development. 2988 1

Glioblastoma (GBM) is a common and aggressive brain tumor that is associated with significant increase in glycolysis for energy production. Icaritin is a natural compound and exhibits anticancer activity in GBM. However, the effect of icaritin on glycolysis in GBM cells remains unclear. The aim of the current study was to investigate the effect of icaritin on glycolysis in GBM cells. The human GBM cell lines U87 and T98G were treated with icaritin or the inhibitor of Stat3 (S3I-201) in the presence or absence of recombinant human interleukin (IL)-6. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The glycolysis was analyzed by detecting the glucose consumption and lactate production. The Western blot analysis was conducted to detect the expressions of hexokinase 2 (HK2), signal transducer and activator of transcription 3 (Stat3), p-Stat3, and B lymphoma Mo-MLV insertion region 1 (Bmi-1). Results showed that icaritin inhibited the viability of U87 and T98G cells in a dose-dependent manner. The decreased glucose consumption and lactate production, accompanied by reduced expressions of HK2, were found in both U87 and T98G cells. Icaritin inhibited the IL-6/Stat3 pathway, which is evidenced by the decreased expressions of p-Stat3 and Bmi-1. IL-6 treatment induced the phosphorylation of Stat3 and Bmi-1 expression, increased cell viability, as well as elevated glucose consumption, lactate production, and HK2 expression; however, the effects of IL-6 were attenuated by icaritin or S3I-201 treatment. In conclusion, icaritin exerted inhibitory effects on cell viability and glycolysis in GBM cells, which was mediated by the IL-6/Stat3 pathway.
 ...
PMID:Icaritin inhibits glioblastoma cell viability and glycolysis by blocking the IL-6/Stat3 pathway. 3039 Mar 36