Synergistic Anticancer Effect of Glycolysis and Histone Deacetylases Inhibitors in a Glioblastoma Model

Autor: Beata Pająk, Ewelina Siwiak-Niedbalska, Anna Jaśkiewicz, Maja Sołtyka, Rafał Zieliński, Tomasz Domoradzki, Izabela Fokt, Stanisław Skóra, Waldemar Priebe
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biomedicines, Vol 9, Iss 12, p 1749 (2021)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines9121749
Popis: Over the last decade, we have seen tremendous progress in research on 2-deoxy-D-glucose (2-DG) and its analogs. Clinical trials of 2-DG have demonstrated the challenges of using 2-DG as a monotherapy, due to its poor drug-like characteristics, leading researchers to focus on improving its bioavailability to tissue and organs. Novel 2-DG analogs such as WP1122 and others have revived the old concept of glycolysis inhibition as an effective anticancer strategy. Combined with other potent cytotoxic agents, inhibitors of glycolysis could synergistically eliminate cancer cells. We focused our efforts on the development of new combinations of anticancer agents coupled with 2-DG and its derivatives, targeting glioblastoma, which is in desperate need of novel approaches and therapeutic options and is particularly suited to glycolysis inhibition, due to its reliance on aerobic glycolysis. Herein, we present evidence that a combined treatment of 2-DG analogs and modulation of histone deacetylases (HDAC) activity via HDAC inhibitors (sodium butyrate and sodium valproate) exerts synergistic cytotoxic effects in glioblastoma U-87 and U-251 cells and represents a promising therapeutic strategy.
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