r-59949 has been researched along with Glioblastoma* in 1 studies
1 other study(ies) available for r-59949 and Glioblastoma
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Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers.
Although diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible factor-1α (HIF-1α) are key targets of DGKα inhibition, in addition to its regulation of other oncogenes. DGKα regulates mTOR transcription via a unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKα inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and melanoma xenograft treatment models, with growth delay and decreased vascularity. This study establishes DGKα as a central signaling hub and a promising therapeutic target in the treatment of cancer. Topics: Apoptosis; Brain Neoplasms; Cell Line, Tumor; Diacylglycerol Kinase; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Targeted Therapy; Piperidines; Pyrimidinones; Quinazolinones; RNA, Small Interfering; Thiazoles | 2013 |