Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bernstock, JD; Ye, D; Gessler, FA; Lee, Y-J; Peruzzotti-Jametti, L; Baumgarten, P; Johnson, KR; Maric, D; Yang, W; Kögel, D; Pluchino, S; Hallenbeck, JM

Published Date

  • August 7, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 7425 -

PubMed ID

  • 28785061

Pubmed Central ID

  • PMC5547153

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-07631-9


  • eng

Conference Location

  • England