Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.
Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.
Duke Scholars
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- Tumor Cells, Cultured
- Topotecan
- Sumoylation
- Immunohistochemistry
- Hypoxia-Inducible Factor 1, alpha Subunit
- Humans
- Glioblastoma
- Enzyme Inhibitors
- Cyclin-Dependent Kinase 6
- Cell Proliferation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Topotecan
- Sumoylation
- Immunohistochemistry
- Hypoxia-Inducible Factor 1, alpha Subunit
- Humans
- Glioblastoma
- Enzyme Inhibitors
- Cyclin-Dependent Kinase 6
- Cell Proliferation