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Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7, 2407-2413 p.Article in journal (Refereed) Published
Abstract [en]

Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

Place, publisher, year, edition, pages
2012. Vol. 32, no 7, 2407-2413 p.
Keyword [en]
Glioblastoma, stem cells, proteasome inhibitor, HDAC inhibitor, TB101, R11 stem cells, U251 MG, GL 15 cells
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-56568OAI: oai:DiVA.org:umu-56568DiVA: diva2:536054
Available from: 2012-06-25 Created: 2012-06-20 Last updated: 2017-12-07Bibliographically approved

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Asklund, ThomasHolmlund, CamillaWibom, CarlBergenheim, TommyHenriksson, RogerHedman, Håkan

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