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Monday, October 16, 2017 10:24:59 AM
used in combination with gefitinib and sertraline for brain cancer treatment (today's PR mentions these combination treatments)
https://www.ncbi.nlm.nih.gov/pubmed/27689322
Case-specific potentiation of glioblastoma drugs by pterostilbene.
Schmidt L1, Baskaran S1, Johansson P1, Padhan N1, Matuszewski D2, Green LC3, Elfineh L1, Wee S4, Häggblad M5, Martens U5, Westermark B1, Forsberg-Nilsson K1, Uhrbom L1, Claesson-Welsh L1, Andäng M4, Sintorn IM2, Lundgren B5, Lönnstedt I1, Krona C1, Nelander S1.
Author information
Abstract
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.
KEYWORDS:
cancer therapeutics; drug repurposing; glioblastoma; glioblastoma initiating cells; stilbenoids
PMID:
27689322
PMCID:
PMC5341973
DOI:
10.18632/oncotarget.12298
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