ArticleJournal of cancer research and clinical oncology2011
Etoposide-mediated glioblastoma cell death: dependent or independent on the expression of its target, topoisomerase II alpha?
Article in Journal of cancer research and clinical oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- Innovative nanoparticle-based therapeutic strategies against glioblastoma multiform: a focus on enhanced delivery systems and efficacy.Frontiers in bioengineering and biotechnology · 2025Review
- Oncofetal HMGA2 attenuates genotoxic damage induced by topoisomerase II target compounds through the regulation of local DNA topology.Molecular oncology · 2019Article
- Topoisomerase II Poisons for Glioblastoma; Existing Challenges and Opportunities to Personalize Therapy.Frontiers in neurology · 2018Review
- Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells.Molecular pharmaceutics · 2016Article
- A role for epigenetics in the formation of chromosome translocations in acute leukemia.Cancer genetics · 2015Review
- Convection-enhanced delivery of etoposide is effective against murine proneural glioblastoma.Neuro-oncology · 2014Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatments which significantly improve progression-free and overall survival for patients with relapsed glioblastoma (GBM) after the standard therapy are lacking. The Topoisomerase II (TopoII) enzyme is a key target of anticancer agents because of the important role it plays in transcription regulation and chromatin remodeling. A drug with strong topoisomerase-mediated anticancer activity is etoposide that is used in combination with carboplatin in patients with relapsed GBM. We hypothesized that tumors harboring high expression of TopoII alpha (TopoIIa) would be more sensitive to etoposide treatment.
methodsThe relative expression levels of TopoIIa protein were measured in a panel of GBM cell lines using Western blot analysis and in a cohort of GBM using immunohistochemistry. Expression levels of TopoIIa in the cell lines were correlated with relative sensitivity to treatment with etoposide. To ascertain the role TopoIIa plays in mediating response to etoposide, expression was reduced with a siRNA targeted to TopoIIa.
resultsProtein expression of TopoIIa, although high in the cell lines, was very low in patient specimens. Correlations between TopoIIa protein expression and sensitivity to etoposide were evident. The IC(50) for the low-TopoIIa-expressing cell line, T98G, was almost 50 times higher than M059K (high TopoIIa). Inhibition of TopoIIa in MO59K cells with siRNA significantly altered the IC(50), increasing the resistance to etoposide. Interestingly, the expression of TopoIIa was not decreased after treatment with etoposide, indicating other mechanisms underplay treatment response.
conclusionsIn vitro, the levels of TopoIIa protein expression correlate with response to etoposide but also multiple molecular events namely DNA-PK and MDR also play a role in cell sensitivity to etoposide. That we did not find a high expression of TopoIIa in clinical specimens further suggests the mechanisms underlying treatment response are complex.
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