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

Publication ,  Journal Article
Bernstock, JD; Ye, D; Gessler, FA; Lee, Y-J; Peruzzotti-Jametti, L; Baumgarten, P; Johnson, KR; Maric, D; Yang, W; Kögel, D; Pluchino, S ...
Published in: Sci Rep
August 7, 2017

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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 7, 2017

Volume

7

Issue

1

Start / End Page

7425

Location

England

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
 

Citation

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Bernstock, J. D., Ye, D., Gessler, F. A., Lee, Y.-J., Peruzzotti-Jametti, L., Baumgarten, P., … Hallenbeck, J. M. (2017). Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming. Sci Rep, 7(1), 7425. https://doi.org/10.1038/s41598-017-07631-9
Bernstock, Joshua D., Daniel Ye, Florian A. Gessler, Yang-Ja Lee, Luca Peruzzotti-Jametti, Peter Baumgarten, Kory R. Johnson, et al. “Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.Sci Rep 7, no. 1 (August 7, 2017): 7425. https://doi.org/10.1038/s41598-017-07631-9.
Bernstock JD, Ye D, Gessler FA, Lee Y-J, Peruzzotti-Jametti L, Baumgarten P, et al. Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming. Sci Rep. 2017 Aug 7;7(1):7425.
Bernstock, Joshua D., et al. “Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.Sci Rep, vol. 7, no. 1, Aug. 2017, p. 7425. Pubmed, doi:10.1038/s41598-017-07631-9.
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. Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming. Sci Rep. 2017 Aug 7;7(1):7425.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 7, 2017

Volume

7

Issue

1

Start / End Page

7425

Location

England

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