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Review Article

Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment

Author(s): Rawan Nehme, Rawan Hallal, Maya El Dor, Firas Kobeissy, Fabrice Gouilleux, Frédéric Mazurier and Kazem Zibara*

Volume 28, Issue 11, 2021

Published on: 08 September, 2020

Page: [2218 - 2233] Pages: 16

DOI: 10.2174/0929867327666200908114411

Price: $65

Abstract

Drug repurposing has lately received increasing interest in several diseases especially in cancers, due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins, including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways known for their role in cell proliferation and survival, such as the JAK/STAT pathway. CML therapy, based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However, 15% of patients are refractory to IM, where in some cases, 20-30% of patients become resistant. Thus, we suggest the repurposing of ACF in CML after IM failure or in combination with IM to improve the anti-tumor effects of IM. In this review, we present the different pharmacological properties of ACF along with its anti-leukemic effects in the hope of its repurposing in CML therapy.

Keywords: Acriflavine, ACF, drug repurposing, chronic myeloid leukemia, leukemia, anti-tumoral, anti-leukemic.

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