HIF-1α- Targeting Acriflavine Provides Long Term Survival and Radiological Tumor Response in Brain Cancer Therapy

Antonella Mangraviti, Tula Raghavan, Francesco Volpin, Nicolas Skuli, David Gullotti, Jinyuan Zhou, Laura Asnaghi, Eric Sankey, Ann Liu, Yuan Wang, Dong Hoon Lee, Noah Gorelick, Riccardo Serra, Michael Peters, Destiny Schriefer, Fabien Delaspre, Fausto J Rodriguez, Charles G Eberhart, Henry Brem, Alessandro OliviBetty Mae Tyler

Research output: Contribution to journalArticle

Abstract

Tumor progression, limited efficacy of current standard treatments, and the rise in patient mortality are associated with gene expression caused by the synergistic action of intratumoral hypoxia and HIF-1α activation. For this reason, recent investigations have focused on HIF-targeting therapeutic agents, with encouraging preclinical and clinical results in solid tumors. Here we describe the efficacy of a HIF-1α inhibitor, Acriflavine, and demonstrate its potency against brain cancer. This safe antibacterial dye induces cell death and apoptosis in several glioma cell lines, targets HIF-1α-mediated pathways, and decreases the level of PGK1, VEGF and HIF-1α in vitro and in vivo. Administered locally via biodegradable polymers, Acriflavine provides significant benefits in survival resulting in nearly 100% long term survival, confirmed by MRI and histological analyses. This study reports preclinical evidence that this safe, small molecule can contribute to brain tumor therapy and highlights the significance of HIF-1α-targeting molecules.

Original languageEnglish (US)
Article number14978
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

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    Mangraviti, A., Raghavan, T., Volpin, F., Skuli, N., Gullotti, D., Zhou, J., Asnaghi, L., Sankey, E., Liu, A., Wang, Y., Lee, D. H., Gorelick, N., Serra, R., Peters, M., Schriefer, D., Delaspre, F., Rodriguez, F. J., Eberhart, C. G., Brem, H., ... Tyler, B. M. (2017). HIF-1α- Targeting Acriflavine Provides Long Term Survival and Radiological Tumor Response in Brain Cancer Therapy. Scientific Reports, 7(1), [14978]. https://doi.org/10.1038/s41598-017-14990-w