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Cited by 46Ubiquitin and proteasome pathwaysGlioma Diagnosis and TreatmentProtein Degradation and Inhibitors

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

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Bernstock, Joshua D., Ye, Daniel, Gessler, Florian A., Lee, Yang-ja, Peruzzotti-Jametti, Luca, Baumgarten, Peter, Johnson, Kory R., Maric, Dragan +4 more·2017·Scientific Reports
DOI 10.1038/s41598-017-07631-9PMC PMC5547153
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Abstract

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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  • Altered SUMO conjugation may contribute to reduced HIF-1α protein levels.

    “Because SUMOylation enhances both the stability and transcriptional activity of HIF-1α [190], altered SUMO conjugation may contribute to reduced HIF-1α protein levels.”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [315]

    The Discussion (page unavailable) reports that some studies find SUMOylation stabilizes HIF-1α and enhances its transcriptional activity, but others find the opposite. The Results report reduced HIF-1α protein after topotecan treatment alongside perturbed SUMOylation; they do not establish that altered SUMO conjugation caused the reduction. Thus the proposed contribution is plausible, but the citing sentence presents a contested premise as settled. (LLM, conf=0.83)

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  • Topotecan has also been reported to inhibit global protein SUMOylation.

    “This interpretation warrants caution, as topotecan has also been reported to inhibit global protein SUMOylation [315].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [315]

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Authors
Bernstock, J. D., Ye, D., Gessler, F. A., Lee, Y.-J., Peruzzotti-Jametti, L., Baumgarten, P., Johnson, K. R., Maric, D., Yang, W., Kögel, D., Pluchino, S., & Hallenbeck, J. M.
Affiliations
  • National Institutes of Health (US)
  • Goethe University Frankfurt (DE)
  • Duke Medical Center (US)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
Corresponding author
Bernstock, Joshua D.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-08-07
Volume
7
Issue
1
Pages
7425-7425
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-07631-9
PMC
PMC5547153
OpenAlex
W2740765687
Cited by
46
References
4
Citations by year
2026: 6 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 2 · 2017: 2
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust
  • Cambridge Trust
  • Gates Cambridge Trust
  • National Institutes of Health
  • Medical Research Council (MC_PC_12009)
  • National Institute of Neurological Disorders and Stroke
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
topotecan, SUMOylation, glioblastoma, SUMOylation inhibitors, CDK6, HIF-1α, cell cycle progression, cellular metabolism, post-translational modification, adjuvant therapy
MeSH terms
Antineoplastic Agents, Cell Cycle, Enzyme Inhibitors, Glioblastoma, Humans, Immunohistochemistry, Tumor Cells, Cultured, Blotting, Western, Topotecan, Cell Proliferation, Cyclin-Dependent Kinase 6, Hypoxia-Inducible Factor 1, alpha Subunit, Sumoylation

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