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Case-specific potentiation of glioblastoma drugs by pterostilbene
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Number of Authors: 20
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, 73200-73215 p.Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.

Place, publisher, year, edition, pages
2016. Vol. 7, no 45, 73200-73215 p.
Keyword [en]
glioblastoma, glioblastoma initiating cells, stilbenoids, drug repurposing, cancer therapeutics
National Category
Cell Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-136745DOI: 10.18632/oncotarget.12298ISI: 000387452100060OAI: oai:DiVA.org:su-136745DiVA: diva2:1056868
Available from: 2016-12-15 Created: 2016-12-14 Last updated: 2016-12-15Bibliographically approved

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Martens, UlfLundgren, Bo
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Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
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