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

Scientific Reports
Antonella MangravitiBetty Tyler

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.

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Citations

Aug 31, 2018·Journal of Neurosurgical Sciences·Evgenii BelykhPeter Nakaji
Jan 24, 2020·Expert Opinion on Drug Delivery·Nagat El DemerdashBetty Tyler
Jul 16, 2020·Journal of Cellular and Molecular Medicine·Rawan HallalFrédéric Mazurier
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Oct 28, 2020·British Journal of Cancer·Carolina BernauerJanet M Shipley
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Methods Mentioned

BETA
flow cytometry
fluorescence imaging
FACS

Software Mentioned

GrapPad
GraphPad Prism
FlowJo

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